During a rainy night, a fishing boat is attacked by a giant octopus. The giant octopus is then attacked by a giant green-haired humanoid monster. After defeating the giant octopus, the green monster then attacks the boat. A survivor is recovered, who reveals to doctors and police that Frankenstein attacked his boat and ate the crew. The press picks up the story and interviews Dr. Paul Stewart and his assistant, Dr. Akemi Togawa, who once had a baby Frankenstein in their possession for study five years prior. Stewart and Akemi dispel the idea that the attack was caused by their Frankenstein, postulating that their Frankenstein was gentle, would not attack nor eat people, nor would he live in the ocean as he was found in the mountains and likely died after he escaped.
Another boat is attacked and villagers see the green Frankenstein off the coast at the same time that a mountain guide reports seeing Frankenstein in the Japanese Alps. Stewart and Akemi investigate the mountains and find giant footprints in the snow. Their colleague, Dr. Majida, collects tissue samples from the second boat. The green Frankenstein attacks Haneda Airport, eats a woman and returns to the sea after the clouds clear. Stewart and Akemi leave for Tokyo for a meeting with the military to discuss plans to kill the monster. Majida deduces that the green Frankenstein is sensitive to light. The green Frankenstein briefly appears in Tokyo, but is driven away by bright lights. It retreats to the mountains, where the military counterattacks it. Then a second Frankenstein, brown-haired in appearance, appears and comes to the green Frankenstein's aid, helping it escape.
Stewart and Akemi conclude that the brown Frankenstein is their former subject. To distinguish the monsters, the military designate the brown and green Frankensteins as Sanda and Gaira, respectively. After collecting and examining tissue samples from both monsters, Stewart concludes that Gaira is Sanda's clone. He theorizes that a piece of Sanda's tissue made its way out to sea, where it survived off plankton and evolved into Gaira. During a hiking trip, Stewart, Akemi and several hikers run away from Gaira. Akemi falls off a ledge, but Sanda saves her in time, injuring his leg in the process. Stewart and Akemi try to convince the military that only Gaira should be killed while Sanda should be spared, but the army ignores their pleas, unwilling to risk letting either monster live. After discovering that Gaira devoured people, Sanda attacks him. Gaira escapes with Sanda pursuing and heads towards Tokyo, no longer deterred by the city lights as they alert him to the presence of food.
During the evacuation, Akemi vows to save Sanda, but runs into Gaira instead. Sanda stops Gaira from devouring Akemi and Stewart carries her to safety. Sanda tries to plead with Gaira, but the green monster engages Sanda in battle. Stewart tries to convince the military to give Sanda time to defeat Gaira, but fails. However, the military aids Sanda as his battle with Gaira moves from Tokyo to Tokyo Bay and further out to sea. As the military drops bombs around the battling Frankensteins, an underwater volcano suddenly erupts, swallowing up both monsters. Majida informs Stewart and Akemi that the monsters' deaths could not be confirmed due to the intense heat, but stresses that nothing could have survived the eruption.
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