In the year 1968, every day is the same for Dr. Robert Morgan: he wakes up, gathers his weapons and then goes hunting for vampires. Morgan lives in a world where everyone else has been infected by a plague that has turned them into undead, vampiric creatures that cannot stand sunlight, fear mirrors, and are repelled by garlic. They would kill Morgan if they could, but fortunately, they are weak and unintelligent. At night, Morgan locks himself inside his house; during the day, he kills as many vampires as he can, burning the bodies.
A flashback sequence explains that, three years before, Morgan's wife and daughter had succumbed to the plague, before it was widely known by the public that the dead would return to life. Instead of taking his wife to the same public burn pit used to dispose of his daughter's corpse, Morgan buried her without the knowledge of the authorities. When his wife returned to his home and attacked him, Morgan became aware of the need to kill the plague victims with a wooden stake. Morgan hypothesizes that he is immune to the bacteria because he was bitten by an infected vampire bat when he was stationed in Panama, which introduced a diluted form of the plague into his blood.
One day, a dog appears in the neighborhood. Morgan chases after the dog but does not catch it. Some time later, the dog appears, wounded, at Morgan's doorstep. He takes the dog into his home and treats its wounds, looking forward to having company for the first time in three years. He quickly discovers, however, that it too has become infected with the plague. Morgan is later seen burying the dog, which he has impaled with a wooden stake.
While out on his daily rounds, Morgan spots a woman in the distance. The woman, Ruth, is terrified of Morgan at first sight, and runs from him. Morgan convinces her to return to his home, but is suspicious of her true nature. Ruth becomes ill when Morgan waves garlic in her face, but claims that she has a weak stomach.
Morgan's suspicion that Ruth is infected is confirmed when he discovers her attempting to inject herself with a combination of blood and vaccine that holds the disease at bay. Ruth initially draws a gun on Morgan, but surrenders it to him. Ruth then tells him that she is part of a group of people like her — infected but under treatment — and was sent to spy on Morgan. The vaccine allows the people to function normally with the drug in the bloodstream, but once it wears off, the infection takes over the body again. Ruth explains that her people are planning to rebuild society as they destroy the remaining vampires, and that many of the vampires Morgan killed were technically still alive.
While Ruth is asleep, Morgan transfuses his own blood into her. She is immediately cured, and Morgan sees hope that, together, they can cure the rest of her people. Moments later, however, Ruth's people attack. Morgan takes the gun and flees his home while the attackers kill the vampires gathered around Morgan's home.
Ruth's people spot Morgan and chase him. He exchanges gunfire with them, and picks up tear gas grenades from a police station armory along the way. While the tear gas delays his pursuers somewhat, Morgan is wounded by gunfire and retreats into a church. Despite Ruth's protests to let Morgan live, his pursuers finally impale him on the altar with a spear. With his dying breaths, Morgan denounces his pursuers as "freaks," and declares that he is the last true man on earth.
- Vincent Price as Dr. Robert Morgan
- Franca Bettoia as Ruth Collins
- Emma Danieli as Virginia Morgan
- Giacomo Rossi-Stuart as Ben Cortman
- Umberto Raho as Dr. Mercer
- Christi Courtland as Kathy Morgan
- Antonio Corevi as the Governor
- Ettore Ribotta as the TV Reporter
- Rolando De Rossi
- Carolyn De Fonseca dubbed for Ruth Collins' voice in the English release of the film. She was uncredited.
- Giuseppe Mattei as the leader of the survivors. He was also uncredited.
- If one looks closely, in a shot of Morgan driving back to his vampire-besieged home at night, it is daytime.