1948, in the darkest, unexplored depth of the wild Amazon River, rumors abound about native tribes vanishing and strange lights being reported by passing cargo planes. Doc Atlas and his comrades are asked by a long time friend of Doc's late father to find his missing playboy son who disappeared in the region.

At the same time, Doc's aide Mad Dog Deagan learns that the man who saved his life during the War is in need of assistance on a rescue mission that is also seeking the playboy adventurer. In the meantime, ace reporter Penny Cartier, Doc's girlfriend, secretly travels to the Amazon to investigate the story of the missing millionarie.

Doc and company not only face treachery of the human kind, but also must confront a flame-breathing cyclops and a diabolical ritual that causes men's skin to erupt in jade boils inflicting the horrifying Green Death.