In postwar Vienna, Austria, Holly Martins, a writer of pulp Westerns, arrives penniless as a guest of his childhood chum Harry Lime, only to learn he has died. Martins develops a conspiracy theory after learning of a "third man" present at the time of Harry's death, running into interference from British officer Major Calloway, and falling head-over-heels for Harry's grief-stricken lover, Anna.

In the summer of 1928, the Scottish physician Alexander Fleming discovered penicillin by accident, but it would take two more decades and a world war before he and others succeeded in producing the antibiotic in such large quantities as to eradicate the epidemics of the time: typhus, syphilis, gangrene and tuberculosis.