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On a peacetime patrol in the Pacific, the U.S. Navy's atomic submarine, captained by Commander Pete Mathews, is chased and held by an enormous, unidentifiable object. The sub picks up strong radioactive signals from outside the ship, but Pete's evasive maneuvers eventually wrench the vessel free. Upon returning to the Pearl Harbor naval base in Honolulu, a strange substance is discovered lodged on the ship's plates, prompting the Defense Department to summon two marine biology experts, Dr. John Carter and Dr. Lesley Joyce, to the base. After an initial exam, both Lesley and John agree that the substance came from a living creature, despite Pete and the Navy's incredulity. Over the following two weeks, as John and Lesley continue their investigation, Pete shows a personal interest in Lesley, who is only anxious to return to her own research. Finally, John and Lesley present their findings, stating that their tests suggest that the submarine was attacked by a giant octopus, which apparently was disturbed from its nest deep in the Pacific's Mindanao Straights by radioactive contamination from the atomic bomb fallout over Japan. Lesley explains that the unusual radioactive charge given off by the creature alerts its prey of its approach, and in desperation the octopus has surfaced in search of food. John and Lesley speculate that unexplained disappearances of a Japanese fishing fleet and a Siberian seal boat may have been due to the octopus. Pete and the Navy representatives express doubt over this hypothesis, however, and demand further proof. Later, as Pete assists John and Lesley with departure arrangements, a report comes in of an attack on a French shipping boat, from which several men escaped in a raft. John and Lesley are once again pressed into service for the government. The French survivors are questioned by psychiatrists, but when the first sailor's description of an attack by a creature with giant tentacles is met with skepticism, the other sailors refuse to testify. Lesley is able to convince the first sailor to repeat his story for the government officials, who now have the evidence they need to back up the scientists' premise. The government then halts all sea traffic in the North Pacific without revealing the reason to other countries. John flies out to sea to trace a missing ship, while Pete and Lesley follow up a report of three missing people on the coast of Oregon. The local sheriff, Bill Nash, takes them to the site of the attack along the beach, where they find a giant suction imprint in the sand and request that John join them. While waiting, Pete and Lesley fish all day to no avail, and are convinced that the giant creature may be in the vicinity. After John arrives and the imprint is definitively identified as octopus, Pete demands Lesley leave the project, which now threatens to become dangerous, but she steadfastly refuses. When Bill is attacked along the beach by the creature in front of the scientists, they hastily arrange for the entire Pacific coast waters to be mined before departing for San Francisco and the Navy's central headquarters. An electrified safety net is strung underwater across the entrance to San Francisco Bay to protect the Golden Gate Bridge, which is also wired. John takes a helicopter along the shore and baits the sea with dead sharks in an effort to lure the octopus back inland. Lesley demonstrates to reporters a special jet-propelled atomic torpedo, with which they hope to shoot the creature and then drive it to sea before detonating the device. Later that day, the giant octopus demolishes the net across the Bay and heads toward San Francisco. The Navy orders the Golden Gate Bridge abandoned, but when John learns that the electric circuit on the bridge remains on, races out to shut it off. The bridge is attacked by the creature, but Pete rescues John before one section collapses. The residents of the city panic and begin a mass exodus down the peninsula, as the Navy struggles to evacuate the Embarcadero, which is then battered by the octopus. When several more people are attacked, the Defense Department authorizes Pete to launch his submarine and the atomic warhead. John joins Pete while Lesley remains at the base. Flame throwers push the octopus back into the sea, but when Pete shoots the creature, it grabs the submarine. Using an aqualung, Pete swims out to the octopus and places explosive charges on it before being knocked out by the creature's flailing arms. John then swims out, shoots the octopus in the eye, forcing it to release the ship, and pulls Pete to safety. Back at the base, as the creature turns toward open sea, the torpedo is detonated, destroying the giant octopus. Later, while celebrating, Lesley agrees to continue seeing Pete after she and John finish their next research project.