The story's protagonist is a man named Harker Brayton. He is staying at the home of a friend of his, a scientist named Dr. Druring who keeps several snakes in another wing of his house. Brayton sees a snake under his bed. He finds that the serpent's eyes have a hypnotic effect on him.
An abridged version of "The Man and the Snake" is read by Christopher Lee in the fourth episode of the five-part British radio horror anthology series Christopher Lee's Fireside Tales. The episode first aired on BBC Radio 2 on December 29, 2004.
Harker Brayton spends a long time traveling abroad. When he returns to San Francisco at the age of thirty-five, he stays at the home of his friend Dr. Druring. Dr. Druring is an eminent scientist. He has a large collection of insects, toads and snakes. He keeps them in a separate wing of his house that he calls the Snakery. Dr. Druring does not allow his wife or his daughter to enter the Snakery. This does not bother them because they do not share Dr. Druring's fascination with the creatures that inhabit it. Some snakes, however, sometimes escape from the Snakery and find their way to other parts of the house.
One day, Harker Brayton is in his bedroom in Dr. Druring's house. Brayton is reading a very old science book. According to the book, snakes have the power to hypnotize animals and people so that they can kill them by biting them. Brayton laughs at the thought that scientists once believed such nonsense. He notices two small points of light under his bed. Looking more closely, he sees that they are the eyes of an enormous snake. Brayton does not know if the snake is dangerous or not. He decides, however, that it is best to leave the room, He intends to walk out of the room backwards so as not to startle the snake. He keeps looking at the snake's eyes. He then finds that he cannot move.
As he continues to look into the snake's eyes, Brayton sees visions of a vast landscape. In the center of the landscape is a huge snake wearing a crown. It looks at Brayton with the eyes of his dead mother. Brayton falls to the floor, breaks his nose and cuts his lip. The fall having made Brayton lose eye contact with the snake makes him think that he will now be able to escape from the room. He cannot, however, forget that the snake is there. He looks into its eyes again and his body begins to convulse.
In the library of his house, Dr. Druring is talking to his wife. Dr. Druring is happy because he has recently acquired a snake that eats other snakes. His wife asks him if it catches the other snakes by hypnotizing them. Dr. Druring is somewhat annoyed by the question because he hates it when people refer to the popular misconception that snakes hypnotize their prey. Dr. Druring and his wife then hear some horrible cries coming from Brayton's bedroom. They rush into the room and find him dead as a result of having had a fit. Dr. Druring notices the snake under the bed and says, "how did this get in here?" He takes the snake out from under the bed and throws it onto the floor. It is a stuffed toy snake with two buttons for eyes.