House and his team have a difficult challenge when a teenage boy enters the hospital severely burned with unusual blood-test results. How can you diagnose a burn victim when you cannot use standard testing methods? House makes himself the guinea pig in his own unofficial tests of a new drug designed to treat migraines to prove a former medical school colleague is wrong about the drug.

When Henry experiences a seizure but is not aware of it while it's happening, House takes on the case. The team's differential diagnosis points to a bacterial infection, but Henry suffers a heart attack before the treatment for his infection can work, prompting the need for a heart transplant. Then, the team races to diagnose a dead woman's illness so they can harvest her heart to save their living patient.