Trampas and Pick Lexington visit old friends in Mexico. Trampas is caught between Pick and one of his Mexican friends as both men fall for the same girl. He hopes to stop them from dueling each other while the girl chooses between them.

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In nearly abandoned Spencer Flats, Trampas is held by Della and Annie Spencer, who accuse him of being outlaw Deke Slaughter, though their handyman is not so convinced. Then the real Slaughter rides into the town, claiming to be a sheriff.

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MacKenzie meets a girl in a daze who is thrown off her horse. He takes her to the cabin of the hermit Muley. Initially, the girl doesn't react to them but she slowly recovers some memory. A stranger arrives saying she is wanted for murder.

Betsy Garth is driven by Randy to Brynmar Hall, a large mansion, where she meets several other old acquaintances and invitees (Brooke Bundy, Tom Skerritt, Mark Goddard). All knew Mildred Brynmar, a young woman who was killed in a fire two years before, and have been invited to the house by Mildred's mother (Jane Wyman). A masked figure spies on the proceedings and several mysterious events occur which culminate in death.

Morgan Starr and Randy Benton travel to sell a herd of cattle to an Indian agent to feed the Dakota, but find themselves on a journey of loss and finding, resulting in a change for many lives but especially for Randy.

Starr with Trampas agrees to go to Mexico to check the security of a town where A US Senator and a Mexican Governor plan to sign a treat. All looks okay so Trampas leaves but Starr soon finds he is in the middle of an assassination plot.

The Virginian rescues a man who has been shot. As he recovers at Shiloh he and the Grainger kids realize the man is a bit different as well as being from England. A private detective looking for him provides a clue to his background.

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Twin sisters Judith (Carol Lynley) and Susan (Shirley Knight) Morrow, who are the daughters of a deceased friend of Judge Garth, come to Medicine Bow where Susan is to start a pottery. Also arriving on the same train is a sailor, Kevin Doyle (Tom Tryon) who wants to settle down and become a farmer. While Susan is more reserved and practical, Judith dreams of seeing exotic places and is captivated by Kevin's stories of travel to faraway lands. They begin seeing each other but Judith seems to act strangely. Kevin finds himself so in love with Judith that he agrees to give up his dreams of settling down and take her to the places she has always wanted to see...but her problems are such that this will never come to be.

A cougar kills a Shiloh hand and Steve Hill, experienced in hunting these animals, tracks it into the mountains where he comes upon a homestead owned by Nancy Mayhew (Joyce Bulifant) and her husband Charles (Jack Klugman). The Mayhew's have strained relations and it is learned Charles son was killed by the same cougar. Nancy blames this on Charles' cowardice and indicates a romantic interest in Steve, an interest which eventually endangers Steve's life.

Trampas wins a steamboat in a poker game on a steamboat but the money is confiscated for being stolen. When he tries to collect on the steamboat he won, he finds himself involved with an outlaw gang and a crooked boat owner.

Molly Wood (Pippa Scott) tells Trampas of the outbreak of the Spanish-American war and says she is impressed with a man in uniform, so Trampas rides to San Antonio, Texas to join the Rough Riders being formed by Teddy Roosevelt. Steve Hill and the Virginian follow, intent on persuading Trampas to return but they both end up enlisting as well despite conflicts between the free-sprited westerners and their staid eastern officers led by Lt. Drex (Ray Danton). In Cuba, when Lt. Drex is wounded, the Virginian leads a detail including Steve and Trampas to discover and decommission snipers and a hidden cannon emplacement, which they manage to do successfully. After the three soldiers return to Medicine Bow, they learn a welcome home party is going to be held in the Town Hall in their honor.

After delivering a herd of cattle to New Orleans, the Virginian meets and falls for a mysterious woman, Marie Valonne (Madlyn Rhue). He is attacked and the woman disappears. In his attempts to relocate her he comes into conflict with Johnny Madrid (Mark Richman) who controls some corrupt politicians. Despite the assistance of a local police detective, Dan Bohannon (Skip Homeier), the Virginian is unsuccessful in finding Marie and is only left with her picture.

Lars Holstrum (Peter Whitney) is a middle-aged and wealthy rancher friend of Judge Garth's who is about to marry a 20 year old girl. Lars injures his back and Trampas is given the job of traveling to Laramie to pick up the girl, Katia Swenson (Katherine Crawford). On the return trip the two have a series of misadventures revolving around encounters with local Indians, a group of cowpokes, and a mysterious man who has been trailing them from Laramie.

A notorious Civil War criminal defended by Garth arrives in Medicine Bow to join his family. He expects payment from Garth who he believes profited from his case but Garth wants nothing to do with the man but Jennifer befriends the family.

As Ryker leaves town for a few days, a group of men known as Metis arrive in Medicine Bow. They are a rough group but want no trouble. However, the people are afraid of trouble which comes as Starr tries to stop it - from themselves.

Randy's family visits from the hills of Bald Knob to protect him from a Claiborne who has been released from prison. Randy's testimony helped send him to prison. His daughter a childhood friend of Randy complicates his desire for revenge.

Seeking some excitement in his life, Trampas joins a groups of older cowboys (Steve Cochran, James Brown, Claude Akins) who set off to find adventure in what they still believe is the wild, lawless West. However, their outdated attitudes lead them into trouble and eventually, tragedy.

Widower Stavros Karas has agreed with a friend in Greece to marry his daughter. He told his friend he had a nice place but in reality he has little and needs water from his neighbor whose son falls for his young and beautiful bride.

After 35 years in prison Tom Brant returns to Medicine Bow. A newspaper reporter's story about him stirs the interest of people who had various connections to him. People swarm to him for different reasons including the money he hid.

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At the same time the Colonel's niece is visiting from England, Trampas is one of the suspects in the killing of a fellow ranch hand based on his custom gun. Trampas believes four brothers killed their cousin but how can he prove it.