Profondo Rosso follows music teacher Marcus Daly (Hemmings) as he investigates the violent murder of psychic medium Helga Ulmann (Macha Meril), which he witnesses in an apartment building. Other key characters are introduced early, including Daly’s occasional friend Carlo (Gabriele Lavia), Ulmann’s associate Dr. Giordani (Glauco Mauri) and reporter Gianna Brezzi, with whom Daly begins an affair. Brezzi’s character is played by Daria Nicolodi, who would later become Argento’s partner and the mother of his daughter Asia.
In his failed attempt at rescuing the medium, Daly realises he could have seen the killer’s face among a group of portraits on the wall of the victim’s apartment but is unable to find or recognise it when the police arrive. Later in the film, he also initially overlooks another clue that leads him to discover a mouldering corpse walled up in a derelict house. In typical Argento fashion, one murder leads to a string of others as Daly’s obsession with this vital clue that he fails to understand puts his life and those of everyone he comes into contact with in danger. This inability of a character to interpret or comprehend what he has seen is a common theme in Argento’s films and was used repeatedly in Tenebrae.
The killing of Helga Ulmann is prefaced by a child’s doggerel tune, the same piece that accompanies the film’s opening sequence in which two shadowy figures struggle until one of them is stabbed to death. The music serves as the murderer’s calling card. When Daly hears it in his own apartment shortly after becoming involved in the case he is able to foil his attacker. Later, he plays the tune to Giordani, a psychiatrist, who theorizes that the music is important because it probably played an integral part in a traumatic event in the killer's past. The doctor’s theory is of course correct, as the identity of the killer is finally revealed as Carlo’s insane mother Martha (Clara Calamai). When Carlo was still a child, he watched as she murdered her husband when he tried to have her committed, then entomb his body in a room of their house. Daly’s discovery of the corpse is one of the film’s set-pieces.
Argento’s films are known for such elaborate set-pieces of violence and suspense, with meticulous build-up and a visceral study of the mechanics of killing. The murder scenes are generally quite extended: in this film, a female author is stabbed in the spine, then dragged into a bathroom and drowned in a bath filled with scaldingly hot water. Not long afterward, the psychiatrist has his face bashed against a wall, a mantelpiece and a desk before he is finally dispatched with a large knife. The preface to this scene is the movie's signature sequence and possibly its most tension-filled moment. The doctor, alone in his office, is viewed through a window as if being watched, the jarring soundtrack reaches a crescendo and then, when the killer would be expected to burst upon him he is instead accosted by a large doll that approaches him menacingly from the shadows, apparently of its own free will. While Giordani quickly destroys it, the doll is in fact the murderess' calling card and she appears moments later from behind a curtain.
In the climax, Martha confronts Marcus and tries to kill him. Wielding a butchering knife, Martha chases him around the complex and into a room with an elevator. Marcus gets hit in the shoulder by the knife, and, in the process, he kicks Martha toward the elevator shaft. Her excessively long necklace slips in through the crossed metal bars. She tries to pull herself away and, in doing so, the large pendant on the end of the necklace becomes lodged between two small metal bars. As Martha is desperately trying free the necklace, Marcus realizes she is caught and presses the button to activate the lift. It travels downward and the necklace starts choking her tightly. Her hands are clad in leather gloves, making her fingers much too thick to slip in-between her neck and the necklace to try and save herself before it's too late. The elevator provides so much force that the necklace ends up cutting through her neck, decapitating her.
Profondo Rosso is laden with minor details that presage later events. The bathtub murder is foreshadowed by an earlier scene when Daly is lightly scalded by an espresso machine; similarly, Daly explains to Gianni that his psychiatrist once explained that his piano playing is symbolic of him bashing his father’s teeth in, and later in the film Giordani suffers exactly that fate. A child’s doll hanging from a noose and a brief cut to a dog fight (with one dog biting the other by the neck, the other carrying a strange, ghastly gaze) foretell Martha’s aforementioned demise at the end of the film, when the heavy neckchain she is wearing becomes entangled in the bars of an elevator that then ascends, lifting her into the air until she is decapitated. The film also marks the introduction of many of Argento's key hallmarks: discordant soundtracks, odd angles, rolling cameras and various lighting techniques.