On a cold night, an Asian man, Dr. Shimizu, stands out on his back porch when Dr. Barton Saunders emerges from the shadows and kills Shimizu with a contaminated dart. He makes it look like a drunken accident.
The next day, Mike and Jason are testing a new voice-command autopilot system in Airwolf. The system works well, but Mike is reluctant to depend on technology to fly. St. John is taking in a jog with his friend, Dr. Tim Shimizu, a medic who saved St. John from malaria in Vietnam. He gets a call that his father has been in an accident. At the scene, Tim knows that his father's death wasn't an accident, based on the circumstances. He's determined to figure out how he died. At his lab, Tim shows St. John the virus that killed his father under a microscope. Worried that the virus could be spread, he has the crime scene sealed off.
They go back to the crime scene in hazmat suits and sweep the house for traces of the virus, but find nothing. There seems to be no other clues until St. John finds a newspaper article behind a picture frame with Saunders's photo. Saunders took over a failing company called Bar-Med that Shimizu help fund.
At Bar-Med, St. John goes to visit Clive Harper, one of the men in the photo, and he tells St. John a phony story of how Saunders committed suicide when a miracle drug he invented failed to cure his wife. After St. John leaves, a seriously nervous Harper calls Saunders, demanding he be paid and let out of the scheme.
Back at Tim's lab, he tells St. John that the virus was manmade. He then collapses from exposure to the virus. The crew decides to investigate where and how the virus was made. That night, St. John and Jo sneak into Bar-Med, with him checking the grounds and her, the offices, and Mike and Jason cover them in Airwolf. Upon entering Harper's office, Jo finds it ransacked and Harper dead of a contaminated dart to the head. Then Airwolf loses contact with Jo.
As St. John enters a greenhouse, he's watched by Saunders and a bodyguard. Once inside, they shoot him with a contaminated dart containing the virus and he passes out. St. John shocks them when he wakes up a moment later. They take him through a trap door to a hidden lab below the greenhouse. Jo soon enters the greenhouse and cannot determine where they went.
In the secret lab, Saunders explains that his "X-Virus' is a variant of the malaria virus, concentrated, and St. John's immunity is how he survived the dart. Saunders killed Shimizu to prevent him from going to the government with the virus for testing. Bitter, his goal is to inject the plague into general population for personal recognition. St. John tries to escape, but is caught and injected with a more potent form of the virus.
Jo finds the switch to the trap door and enters the secret lab without waiting for the others. She tries to disguise herself in a lab coat, but is caught. St. John is locked inside a room, hands tied. He turns on the light and sees shelves full of lab rats and has them chew his hands free. Jo is then put in the room. Saunders orders his bodyguard to kill St. John and Jo. When he opens the door to the room, the shelves of rats come crashing down on him and St. John and Jo try to escape. It's halted when Saunders shoots a dart into Jo's back, infecting her. As everyone escapes, a lab tech gives St. John the antidote and tells him to fry the building to kill the virus. He injects the antidote into Jo, bringing her back around. After everyone clears the greenhouse, Mike fires a missile, sterilizing the area.
With the last of the virus, Saunders drives into the city and goes to the top of the highest building. Removing the vial from its canister, he maniacally presents it to the city. Mike and Jason arrive in Airwolf and know right away that they can't fire a missile at him in the middle of the city, so they prepare the laser. Jason activates the voice-automated system, but at the last second, Mike lowers his visor and goes to manual. He fires the laser at the vial, causing it and Saunders to explode. Still lacking faith in computerized flying, Mike succeeded in proving that pilots' instinct triumphed over technology in this case.
Later at a pool hall, Tim has recovered and reveals that Saunders's antidote is being used to treat malaria victims. At the pool table, Jason and Mike trade shots to one-up each other. They both miss.