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Tracking two lost lumberjacks through the night, a rescue team nearly follows a hound over a cliff. Two men rappel down to retrieve the fallen hound, but they are killed. The third, hearing screams down below, rappels down to investigate where he finds his teammates dead and is killed by an unseen creature.
Dr. Robert Verne (Robert Foxworth) is fed up with dealing with the squalor of city tenements, where he feels he isn't making a difference. He accepts a job from the Environmental Protection Agency to write a report on a logging operation near the Androscoggin River in Maine. The loggers are in a dispute with the local American Indian "Opies" (i.e., "O.P.s"), the original people. Dr. Verne's wife Maggie (Talia Shire) accompanies him on the trip. She is pregnant, but is apprehensive to tell her husband as he against having children. When flying in, they meet Travis Nelson (Burke Byrnes) and his two children Paul and Kathleen who are embarking on a trek into the wilderness. They also meet paper mill director Bethel Isely (Richard A. Dysart), who is to be their host. He tells them about his missing rescue team and lays the blame at Opies. The latter have their own explanation; Katahdin, a vengeful spirit of the forest that has been awakened by the activities of the loggers, which Isely describes as "larger than a dragon with the eyes of a cat". As Isely drives the couple to their cabin, their path is barred by a party of Opies who refuse to let Isely's people pass and a fight ensues between the leader of the Opies John Hawks (Armand Assante) and Kelso (Everett Creach), one of Isely's heavies. The heavy is armed with a chainsaw while Hawks has only a double-bit axe. The scuffle ends with Hawks laid on the ground with the chainsaw nearly at his throat, causing the Opies to relent and let the cars pass. Verne and Maggie are then shocked by the incident.
While fishing, Verne sees a huge salmon devour a duck. Later, they are attacked in their cabin by a deranged raccoon where he kills it and sends an awaiting tissue sample. The next day Hawks and his wife Ramona (Victoria Racimo) approach Dr. Verne about their side of the story. If Verne is concerned about the environment then he should include the people in his assessment. Something is causing the people to be ill such as still births, mental illness and birth defects. Hawks takes Verne and Maggie to the home of Hector M'Rai (George Clutesi), Ramona's grandfather. Hector claims to have seen Katahdin and describes him as "part of everything in God's creation". Verne sees plant roots growing on the surface that should be underground; Hawk nets a bullfrog-sized tadpole from the water to show Verne; Hector has cigarette burns on his hand but feels no pain. As the evidence mounts, the idyllic setting gradually takes on a sinister hue. Verne and Maggie tour the paper mill to look for incriminating evidence, but the chemicals used in the processing are demonstrated to never leave the plant. Isely tells them that the water is routinely tested for purity. As they leave, Verne however notices mercury deposits on Maggie's boots; a mutagen that causes birth defects and progressive nerve damage. It has long been used in logging as a fungicide due to its cheap value and it will not show up in Isely's water purity tests because it sinks to the bottom. Verne needs more evidence and determines to take blood tests from the Opies.
That night, the Nelson family, who have set up a camp in the woods are suddenly assaulted by Katahdin; a large bear with one of its sides containing horribly mutated skin. The horrified Paul tries to flee, but the beast swats him into a rock and kills him. The next day as Verne and Maggie are taking blood samples, Isely and Sheriff Bartholomew Pilgrim (Charles H. Gray) arrive to arrest Hawks and his men whom they mistakenly believe to be the ones who killed the Nelson family. Hawks however, escapes. Verne, Maggie and Ramona take a helicopter to the campsite to investigate the killings. Verne and Ramona find huge scratch marks on the trees while Maggie finds two mutated bear cubs trapped in a salmon poacher's net, one of them still alive and prompting Verne to save it so it can serve as empirical evidence of the contamination. However, the weather has turned and the pilot Huntoon (Tom McFadden) refuses to take off in the high wind. They set up an emergency room inside one of Hector's tepees and helps the cub survive. A distressed Maggie explains to Verne about her pregnancy and that she has eaten contaminated fish. Isely and Sheriff Pilgrim arrive and see the mutant cub where Isely is contrite, knowing that Hawks and his men didn't commit any crime. Once Hector arrives, Katahdin arrives and attacks the camp in search of her cubs. As everyone else seeks shelter in tunnels beneath Hector's home, Pilgrim is killed by Katahdin when poking his head out.
The next day, the survivors make their way out of the forest. Due to Huntoon's mauled attack, the helicopter is not an option. Isely heads up to Mount Emery to try to reach a radio tower and call for help, but upon arrival is killed by Katahdin. The others find the Opie village abandoned, but they take a truck and drive out along the forest road. At night, Katahdin then attacks the truck and kills Huntoon. In pursuit, the others swim across a river to a log cabin. While swimming, the cub bites Maggie before Verne drowns it. After Katahdin kills Hector, the creature swims underwater where, upon arriving on land, it attacks the cabin. Maggie is knocked unconscious by debris and Ramona is crushed. Verne shoots the creature twice with a rifle with little effect. After Hawks shoots arrows at the bear, he is then killed by the creature's swatting. Once Verne is hoisted up by Katahdin, he stabs it with arrows before collapsing into the lake. Verne then leaps onto the dying Katahdin and continues stabbing it until it dies below the water. The next day, Verne and a surviving Maggie fly over the forest, unbeknownst that another mutant creature (the cubs' father) is still active inside the forest.
Why is the helicopter not an option?
Huntoon's mauled attack