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A Study in Scarlet
Part I leads with a heading which establishes the role of Dr. John Watson as narrator and sets up the narrative stand-point that the work to follow is not fiction, but fact: "Being a Reprint from the Reminiscences of John H. Watson, MD, Late of the Army Medical Department."

The story begins in 1881, when Watson, having returned to London after serving in the Second Anglo-Afghan War, visits the Criterion Restaurant and runs into an old friend named Stamford, who had been a dresser under him at St. Bartholomew's Hospital. Watson confides in Stamford that, due to a shoulder injury that he sustained at the Battle of Maiwand, he has been forced to leave the armed services and is now looking for a place to live-before his six-month half-pay pension runs out. Stamford mentions that an acquaintance of his, Sherlock Holmes, is looking for someone to split the rent at a flat at 221B Baker Street, but he cautions Watson about Holmes's eccentricities.

Stamford takes Watson back to St. Bartholomew's where, in a laboratory, they find Holmes experimenting with a reagent, seeking a test to detect human hemoglobin. Holmes explains the significance of bloodstains as evidence in criminal trials. After Stamford introduces Watson to Holmes, Holmes shakes Watson's hand and comments, "You have been in Afghanistan, I perceive." Though Holmes chooses not to explain why he made the comment, Watson raises the subject of their parallel quests for a place to live in London, and Holmes explains that he has found the perfect place in Baker Street. At Holmes's prompting, the two review their various shortcomings to make sure that they can live together. After seeing the rooms at 221B, they move in and grow accustomed to their new situation.

Watson is amazed by Holmes, who has a profound knowledge of chemistry and sensational literature, very precise but narrow knowledge of geology and botany; yet knows little about literature, astronomy, philosophy, and politics. Holmes also has multiple guests visiting him at different intervals during the day.

After much speculation by Watson, Holmes reveals that he is a "consulting detective" and that the guests are clients. Facing Watson's doubts about some of his claims, Holmes casually deduces to Watson that one visitor, a messenger from Scotland Yard is also a retired Marine sergeant. When the man confirms this, Watson is astounded by Holmes' ability to notice details, assemble them, and draw conclusions.

The Sign of the Four
The story is set in 1888. The Sign of the Four has a complex plot involving service in India, the Indian Rebellion of 1857, a stolen treasure, and a secret pact among four convicts ("the Four" of the title) and two corrupt prison guards. It presents the detective's drug habit and humanizes him in a way that had not been done in the preceding novel, A Study in Scarlet (1887). It also introduces Doctor Watson's future wife, Mary Morstan.

According to Mary, in December 1878, her father had telegraphed her upon his safe return from India and requested her to meet him at the Langham Hotel in London. When Mary arrived at the hotel, she was told her father had gone out the previous night and not returned. Despite all efforts, no trace was ever found of him. Mary contacted her father's only friend who was in the same regiment and had since retired to England, one Major John Sholto, but he denied knowing her father had returned. The second puzzle is that she has received six pearls in the mail from an anonymous benefactor, one per year since 1882 after answering an anonymous newspaper query inquiring for her. With the last pearl she received a letter remarking that she has been wronged and asking for a meeting. Holmes takes the case and soon discovers that Major Sholto had died in 1882 and that within a short span of time Mary began to receive the pearls, implying a connection. The only clue Mary can give Holmes is a map of a fortress found in her father's desk with the names of Jonathan Small, Mahomet Singh, Abdullah Khan and Dost Akbar.

Holmes, Watson, and Mary meet Thaddeus Sholto, the son of the late Major Sholto and the anonymous sender of the pearls. Thaddeus confirms the Major had seen Mary's father the night he died; they had arranged a meeting to divide a priceless treasure Sholto had brought home from India. While quarrelling over the treasure, Captain Morstan—long in weak health—suffered a heart attack. Not wanting to bring attention to the object of the quarrel—and also worried that circumstances would suggest that he had killed Morstan in an argument, particularly since Morstan's head struck the corner of the chest as he fell—Sholto disposed of the body and hid the treasure. However, he himself suffered from poor health and an enlarged spleen (possibly due to malaria, as a quinine bottle stands by his bed). His own health became worse when he received a letter from India in early 1882. Dying, he called his two sons and confessed to Morstan's death and was about to divulge the location of the treasure when he suddenly cried, "Keep him out!" before falling back and dying. The puzzled sons glimpsed a face in the window, but the only trace was a single footstep in the dirt. On their father's body is a note reading "The Sign of the Four". Both brothers quarrelled over whether a legacy should be left to Mary Morstan, and Thaddeus left his brother Bartholomew, taking a chaplet and sending its pearls to Mary. The reason he sent the letter is that Bartholomew has found the treasure and possibly Thaddeus and Mary might confront him for a division of it.