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Nurses are on strike and hold up a delivery man for their allowed 15 seconds. He tries to shove past them but Jeff, accompanying his wife Deb, convulses and collapses. They take him to the hospital E.R., which is crowded due to the strike. House notices Jeff and is intrigued by the fact that Jeff is unceasingly nice. He calls in the team to diagnose Jeff, but they're skeptical that anything is wrong, and suspect House is just trying to prove someone can't possibly be so happy.

With Wilson busy dating Amber, House invites Chase bowling but primarily gripes about Wilson and Amber being together. Chase notes that Cameron had an insufferable friend and they scheduled one night to be with her. House then goes to see Wilson and suggests he share joint custody with Amber. Wilson notes this is (relatively) sane for House, and Amber works out a schedule. However, Wilson refuses to arbitrate.

Foreman and Kutner go over Jeff's house and debate if it's possible for someone to be nice. Kutner notes that House is the exception that proves the rule. Foreman notices hydrofluoric acid among the cleaning supplies and takes a sample.

House and Amber go to Cuddy to arbitrate but she refuses to help out and starts reviewing House's performance. She refuses to give a ruling unless he reviews his team. The tests come back negative but do show low calcium, so House visits Jeff and starts insulting his wife Deb. Jeff remains nice and House concludes he has Williams' Syndrome, a genetic illness that reduces suspicion. Taub and Thirteen note that Jeff doesn't meet any of the other conditions of Williams' Syndrome, shooting a hole in House's theory. However, Jeff suddenly has a stroke.

The team goes into differential, while House runs some very brief performance reviews. Foreman isn't thrilled and eventually gives in to do it himself. House suspects neurosyphilis and Kutner interviews Jeff about his sexual history. He insists that his wife didn't give it to him and he's never had it since he tested negative 10 years ago with the Peace Corps.

House is waiting for Amber and Wilson to arrive when a Watchtower representative stops by his door promising happiness. House isn't impressed. Amber drops off Wilson sixteen minutes late, and House is even less impressed.

Thirteen comes in to see Foreman and proposes heart tests, but he insists on doing her performance review. She'd rather do the tests. Kutner comes in to report the tests are positive for neurosyphilis. Paul insists that it must be him and his test ten years ago must be faulty: he refuses to believe Deb is the source and it must be his fault. She denies having an affair despite the fact there's no other possibility, and notes she'll never be as good as her husband… but tries to be a better person. Kutner warns that as they treat Jeff for neurosyphilis, his attitude toward her may change.

Foreman tries to conduct a performance review with Taub, who refuses to play along and points out that House is simply messing with him by giving him the job. Kutner suspects something is wrong with House. House is out drinking with Wilson and getting him drunk when the team calls with a new diagnosis after Jeff starts vomiting blood. They think he has hepatitis caused by ethanol in his cleansers, or the penicillin they're giving him for the neurosyphilis. He tells them to run more tests and then explains to Wilson that he's getting him drunk to mess up his relationship with Amber. Wilson isn't thrilled and goes back home.

As they run tests and determine Jeff also has hepatitis, Kutner tests House's blood sample and determines that he has syphilis and they go to see House. They tell him they know he has it and House is furious. They provide him with medication and he has nothing else to say as they leave. They explain to Cameron and Chase and conclude that the disease is the reason that House is a jerk, and Chase wonders if Cameron slept with House. They also wonder if House would be less of a doctor if he gets treatment. Cameron refuses to answer Chase's question and he figures she did.

Amber and Wilson meet with House and she objects to the fact House returned Wilson drunk. She concludes House will just get worse until she stops him or stops seeing Wilson. She decides to amend the agreement, adding penalty clauses, and House agrees. House was going to tell Wilson about the syphilis but figures Wilson will tell Amber so doesn't say anything.

Foreman goes to House and insists he formalize his relationship as the team's boss. House insists he wants to humiliate Foreman so that the team will question him, making them better diagnosticians. Foreman isn't buying it.

Deb goes to visit Jeff and he starts snarling at him and then has a heart attack. It's back to differential and House lets Kutner take the marker for the board. Taub suspects that the penicillin is doing its job and causing Jeff's rage. The others have different theories including heart problems and 'roid rage. House let Foreman cast the deciding vote, but he suspects House is setting him up… until House agrees with Foreman's decision. The team is left to wonder if House is better or worse since he didn't participate in the diagnosis.

House goes to Wilson and makes him promise not to tell Amber, then tells him that the team thinks he has syphilis. He slipped them an old blood sample and is faking treatment to fool the team into thinking he's nicer. The two of them go bowling to celebrate.

The team are running tests on Jeff and wondering if they should ease up on House's treatments. However, Amber barges in and announces that Wilson told her House doesn't have neurosyphilis. Kutner confronts House and reveals Amber told him. However, Kutner wonders if Jeff might also have Chagas, which would test positive for neurosyphilis, and that he picked up during his Peace Corps tour in Costa Rica. When they gave him the penicillin, the Chagas flared up, causing the heart attack. Kutner has confirmed his diagnosis with a new MRI.

They go to see Jeff and inform him that he has Chagas Disease, a parasite that caused brain swelling that altered his personality for the last ten years. Deb doesn't believe it and isn't worried that his feelings for her will change.

House goes to see Cuddy and turns in the signed performance reviews. However, she soon figures out they're all the same but admits it's more then she expected. She also discovers he wrote a performance review of her. House insists on reading the rest of the review, and asks her to sign. In response, Amber has demanded that Cuddy deal with the fact that he violated the agreement. He notes that Amber has too and Cuddy insists on implementing penalties on both of them.

Jeff is having a meal with Deb when he notices that the ketchup tastes bad, and wonders what else he doesn't like. Deb is left to wonder.

House and Amber are left changing bed pans… together, while Wilson just smirks.