Shane's plans to establish a school for the homesteaders' children are thwarted by a ruthless rancher (Bert Freed).
An old man whose son has been killed by Shane wants Shane to take his son's place. The albatross-like tenacity of the old man upsets Shane and his guilt reaction is even stronger because he can't remember the face of the man he killed, until the old man shows him a picture.
Shane accepts a job as a gunfighter, despite Marian Starett's protests, to make money to support the Starett family through the winter.
An uncle and three brothers come to town looking to avenge the death of one of their kin, killed during a gun battle with Shane.
While out riding one day, Shane and Marian come upon a sick couple. It's not long before they realize that the couple have contracted a deadly disease. When Marian comes down with the disease, Shane does everything possible to get the quinine they need. He'll do anything - even kill anybody who tries to stand in his way! The drummer that arrives in town decides to make a little profit on the panic that soon erupts.
Two of Rykers' drunken cowhands cause a fire, accidentally killing a young woman. Her husband shoots one of the cowhands, who eventually dies. Ryker announces he's going after the husband who killed his cowhand. Meanwhile, a preacher shows up to perform the funeral service and gets involved. The steps he takes to stop the feud are shocking.