The story begins when a friend of Dr. Watson's wife comes to Watson's house, frantic because her husband, who is addicted to opium, has gone missing. Watson helps her pull him out of the opium den and sends him home. Watson is surprised to find that Sherlock Holmes is there too, in disguise and trying to get information to solve a different case about a man who has disappeared. Watson stays to listen to Holmes tell the story of the case of Neville St. Clair.
St. Clair is a prosperous, respectable, punctual man. His family's home is in the country, but he visits London every day on business. One day when Mr. St. Clair was in London, Mrs. St. Clair also went to London separately. She happened to pass down Upper Swandam Lane, a "vile alley" near the London docks, where the opium den is. Glancing up, she saw her husband at a second-floor window of the opium den. He vanished from the window immediately, and Mrs. St. Clair was sure that there was something wrong.