Flight 627 is flying from Hamburg to Boston when it hits a storm. The seat belt light goes on as one nervous passenger injects himself with insulin. The man seated next to him attempts to reassure him it's just a storm but the man removes his seat belt and moves forward through the cabin. The flight attendant tries to stop him and he turns... his skin is melting off. He throws up into her face and as he staggers through the cabin, the skin of the other passengers starts to melt. The man makes his way forward to the cockpit as the co-pilot looks out, and the pilot engages the auto-pilot. The pilot turns and sees his co-pilot's face falling off.
FBI agents Olivia Dunham and John Scott meet at a hotel and have sex, while worrying that if their boss found out he'd have one of them transferred. John says he loves her and Olivia doesn't respond in kind. They are interrupted by her cell phone from their boss, Charlie Francis. She is called to Logan Airport in Boston and heads out. A few seconds later John gets a call.
Olivia arrives at Logan and Charlie brings her up to speed, informing her that the auto-pilot landed the plane automatically. John arrives, telling someone on his phone that he will treat them like family. At the gate, a man drives up in a van: seemingly the same man who was the first to die on the plane.
Homeland Security Chief Phillip Broyles arrives on behalf of the White House and takes command of the joint-agency task force. He okays Charlie and John to go in. Olivia confronts him and insists she needs to go in so she can function as FBI liaison. He is hostile but allows her to go in with the others, all wearing hazmat suits. They enter the plane and find that all the passengers and crew are dead, their flesh and organs completely liquefied.
The next day at FBI HQ, they go over passengers records after ordering the plane to be incinerated. Broyles is still hostile and suspects terrorism. They get a report that two Middle Eastern men visited a storage facility in Chelsea and handed a briefcase to a Caucasian. Broyles orders her and John to investigate. They arrive at the facility and Olivia notes that Broyles was the friend of a military officer she prosecuted for sexual molestation. Olivia talks to John about their relationship and admits she is in love with him. They kiss and then check a dumpster and find canisters smelling of ammonia. John starts breaking open storage garages. In one they find computer equipment, chemicals, and hairless lab rats. Olivia steps out to get a cell phone signal to call a transport team, while John finds another locker with equipment. A locker behind him opens and the man from the van comes out and runs. John chases after him and calls Olivia for backup. She moves to intercept and the man comes to a halt and takes out his cell phone. Before the two agents can do anything, the mystery man triggers an explosion: John is enveloped in the blast and Olivia is thrown back.
Olivia is taken to the hospital and recovers, but is informed that John is in critical condition. He survived the blast but was doused with synthetic chemical compounds. The doctors keep John unconscious and lower his body temperature. Olivia goes to visit and finds that John's skin is crystallizing.
Olivia checks the files on incidents of dissolving and crystallizing flesh and comes up with a match to a Dr. Walter Bishop. She goes to Broyles with her theory that Bishop is involved. However, Bishop has been in a mental institute for 17 years since his experiments at Harvard resulted in the death of a lab assistant. Broyles is still hostile and comments on his friend whom she prosecuted. However, he insists his decision is not personal and notes that they can't get access to Bishop without the permission of the immediate family. Olivia reveals that Walter has a son, Peter, who is a genius who has gone through a number of different jobs. She goes to Baghdad where Peter is negotiating with Arabic businessmen to get a job. She asks his help to meet with Walter but he refuses. Olivia tries begging and then finally resorts to blackmail, saying she has a file on him. He agrees and they fly back to the U.S., where Peter warns his father was a jerk and did research for a toothpaste company. Olivia notes that Walter was actually working for the U.S. government in the field of "fringe science," but Peter is skeptical.
They get to the mental institute but Peter refuses to see his father initially. Olivia meets with Walter, who is in bad mental shape but was expecting someone to come eventually. He notes that lab animals he worked with suffered similarly and he was able to save them. However, Walter realizes Peter must have let her in and wants to see his son. Peter reluctantly goes in and Walter insists that he has to examine John first-hand. Olivia needs Peter's permission and blackmails him again. Peter agrees but warns her to be careful now that she has what she wants.
As they drive back to Boston, Walter notes that his assistants had access to his research but the only one who knew what he was doing was William Bell, who shared his lab. Olivia and Peter recognize the name: Bell now runs Massive Dynamic, a multi-million dollar company. At the hospital, Olivia asks Charlie to help set up a meeting with Bell. In the medical chamber, Walter examines John and prepares to take a skin sample. Peter stops him but Olivia lets Walter get on with it. He takes the sample and needs to take it to his laboratory in Harvard, but Olivia informs him the lab has been shut down for 17 years. Walter flies into a rage and Pete warns Olivia again that he is dangerous.
Olivia goes to Broyles to get him to open up the laboratory, which is currently being used for storage. He wonders at her determination and suspects that she is involved with John, but she simply repeats her request. They get the authorization and take Walter to the lab where he starts requisitioning equipment and researching an antidote. Peter talks to Olivia and asks about the file she has on him, and then realizes she was bluffing. He admits that he owes money to the mob after he went crazy gambling a couple of years earlier.
Walter has connected the synthetic contagion to a Vietnam weapons research program and concludes that John was exposed to the unprocessed ingredients. He needs a list of the ingredients to manufacture a cure, but John only has 24 hours. Olivia points out that John is the only one who saw the suspect and he is in a coma. Walter notes that he did come up with a process to put two minds in sync so that they could share thoughts and memories. He conducted similar experiments and transferred information from a corpse less than six hours dead. He needs to drug Olivia and insert electrodes into the base of her skull, then put her into a sensory deprivation tank. Olivia agrees, noting that John would do it for her. She has him transferred to the Harvard lab. While she waits, Charlie informs her that Bell is out of the office and it will take them 48 hours to get a court order. She asks him to continue with it if the experiment doesn't work as it is the only other lead they have.
Walter and Peter prepare Olivia and place her in the tank. Along with Olivia's assistant Astrid Farnsworth, they wait as Olivia and John's brain rhythms to synchronize. After several hours, Olivia starts to react and she finds herself in a mental landscape: first a junkyard, then a cemetery, then a bedroom, then FBI headquarters. Finally she finds John and the two kiss. She tries to get him to think back to the storage units and his memories flash through her mind. They get her out of the tank and she goes to the FBI to make an Identikit composite. They match the photo to a passenger on the plane: Morgan Steig. However, his emergency contact is his twin brother, Richard Steig. Steig's last employer was Massive Dynamic.
Olivia goes to Massive Dynamic to see Bell but ends up talking to Nina Sharp, an executive director. She notes that whatever killed the passengers and crew was in Morgan's insulin pen. Sharp agrees to give her all the information on Steig, who was caught stealing field information and fired. She warns that if the FBI drags MD's name into it, they'll sue. Sharp explains that she was a runner who suddenly felt tired a few years ago and Bell ordered a scan. They found cancer and had to amputate Sharp's right arm. The scanning equipment, the drugs, the robotic arm, all were developed by Bell. She turns the file over to Olivia and asks if the FBI agent believes Steig is part of "the Pattern." Olivia doesn't know and Sharp notes that the agent's identification isn't high enough to be informed about it. Sharp warns about the dangers of advancing technology and warns Olivia to be careful.
Olivia gets Steig's home address and calls in an assault team. They break in and find a basement laboratory with more chemical equipment and lab animals. Walter and Peter are waiting outside in the car and Walter worries about Peter's health. He then begs his son not to send him back to the institute. Before Peter can respond, he sees Steig making a run for it. Peter gives chase and Olivia sees him. She chases Steig up through a building and down an alley to where Peter is waiting and captures the suspect.
Olivia interrogates Steig at FBI HQ while Walter and Peter watch on the security monitors. Olivia has no luck and steps out, and Peter slips in. He notes that he can infect Steig with the compound taken from John, any time and any place. He starts smashing Steig's hand despite Olivia's attempts to stop him. Steig gives up the information but Peter warns that John can't absorb the cure before the side effects kill him. Olivia realizes that John has a backup blood supply and they can dissolve the antidote into the stored blood and transfuse it into John. They go ahead with the procedure while Olivia waits outside. Broyles visits and compliments her, noting that "we" are impressed. He warns that there is more involved than simple terrorism and describes dozens of similar fringe science incidents, all part of a Pattern. He wants to offer her a job with unlimited resources to investigate such cases but she just wants things to be they were. Broyles warns that she may not be able to go back.
After a few hours, John recovers consciousness as the crystallization reverses itself. They take him to the hospital for recovery and Olivia visits Steig, who is there for treatment. She wants to know who he's selling his work to but Steig says that an FBI agent threatened him on the phone and Steig recorded the conversation. He tells her where he buried it, outside of his home. Olivia gets the recording and listens to it in the car. Although she can't recognize the voice, she hears a phrase that John used the night he arrived at the airport that she overheard.
At the hospital, John gets out of bed, goes into Steig's room, and smothers the man with a pillow.
Olivia alerts the FBI and drives to the hospital, where she spots John escaping. She gives pursuit and John tries to run her off the road, but his SUV goes out of control. Mortally wounded in the crash, he tells Olivia to question why Broyles sent her to the storage facility. She asks him who he is working with but he dies before he can say anything else.
Like Sharp before him, Charlie notes to Olivia that technology has advanced too fast and too far for them to control, regulate, or protect the people. They return to the lab where Walter and Peter are being escorted away. Olivia tells Peter that his father needs to stay and he needs to stay too. Peter admits that Walter told him about his work and that what happened on the plane is just the beginning. He is considering running... but agrees to stay with his father.
At an underground facility, an attendant brings in John's corpse. Nina Sharp is there, and asks how long John has been dead. The attendant informs her that it has been five hours. She tells the attendant to question John, and the man takes the corpse into a massive facility… with the Massive Dynamic logo.