A young girl on a dive brings up a jar from a sunken slave ship and breaks it, infecting herself with what appears to be smallpox. When House and his team confirm her illness, they call in the CDC, which puts the hospital under quarantine. However, House soon realizes that the girl has something else... but the only way to confirm his diagnosis is to expose himself to the disease. Meanwhile, Wilson and his ex-wife Sam try to tend to a young girl awaiting chemotherapy whose mother is trapped outside by the quarantine.