After a fossilized hand is found in the Amazon, Dr. David Reed gets funding to start an expedition to obtain the rest of the skeleton. Dr. Reed is joined by Dr. Carl Maia, the financial backer Mark Williams, Reed's girlfriend Kay Lawrence and another scientist Dr. Thompson as they board a ship named the Rita to the previous camp where the hand was found, However the site is found destroyed and all the members dead while Dr. Reed's was away. They can't figure who or what could do such a thing but unknown to them a creature known as the Gill Man is watching and stalking (especially over Kay). They head towards the area known as Black Lagoon to continue their research but soon realize the Grill Man threatens their lives.