Ben's ability to close a lucrative livestock contract with a conspicuous widow hinges on the sale of a dilapidated saloon in Upright that Hoss and Joe had impulsively purchased. However, the boys put off the sale when the town drunk (who acts as ""saloon keeper"") insist the crumbling Trails End Saloon may house a fortune. Things get even more complicated when a woman, claiming to be the daughter of the deceased former owner, envisions turning the Trails End into a booming saloon, hotel and restaurant.
The Cartwrights are once again brought in the middle of the Civil War. This time, the wife of former Civil War Col. Cody Ransom brings her young daughter to the Ponderosa, trying to pick up the pieces of their lives. However, Ben soon learns that Col. Ransom may be trying to search for his family. However, Union Maj. Donahue has been pursing Ransom and his men for many years after the war ended, and has refused to accept anybody's terms of surrender - especially since Donahue considers capturing Ransom a personal matter.
Sid Langley is a real estate broker who is not well liked in Nevada, thanks to his shady ways of doing business. An irritable Ben is barely polite with Langley when closing a land transaction. However, things soon get worse than that headache and blurred vision Ben suffers from when he learns that Langley has been critically wounded by an unknown assailant. Ben, who somehow can't remember the past 24 hours, fears he may have been the gunman and tries to reconstruct the activities of the past day to prove his innocence.
A band of ex-Confederate soldiers demands $25,000 from Ben. When Hoss resists their demands and tries to fight them, their leader, Shanklin, shoots Hoss in the abdomen. Hoss lingers near death, and when the doctor is unable to complete the surgery, a nearly inconsolable Ben persuades Shanklin (a confident, competent doctor) to save his son's life. Meanwhile, Jamie - who had witnessed the shooting and nearly got shot himself - searches high and low for Joe, who is involved with a beautiful starlet and intently focused on a poker match.
Ben helps shepherd a young family, the Kosovos (Nick; his wife, Anna; and his son, Sandor), who had recently immigrated from Serbia. Nick soon finds he can't handle the pressure needed to become successful in America and, one evening while Ben is visiting, his mind snaps. He goes on a rampage, trapping Ben (who becomes injured) and a terrified Anna and Sandor inside their home. Ben must do all he can to keep Nick at bay and try to reason with the mentally ill rancher.
Hoss enlists the aid of Judith Coleman, a clairvoyant woman who has the gift of "second sight" to find Jamie. He has been missing in the high country and cannot be found by anyone. Judith's gifted psychic abilities have had a long history of men casting her off as a witch, so at first she is reluctant to help the Cartwrights search for Jamie, then changes her mind since she owes them a great deal. Her fiancee, Jess Avery, who is a minister, doesn't look with favor as to her abilities and she may face the consequences of losing him unless she finds Jamie. Hoss refers to Jamie as his "little brother" for the first time.
Joe is stranded in the desert when his mare falls and breaks her leg. He falls unconscious from exhaustion and lack of water, and is found near death by a Paiute named Swift Eagle. But instead of saving Joe, Swift Eagle steals his gun and goes back to the reservation. His grandfather, Chief Red Cloud, finds the gun and insists they return it and help the owner. Red Cloud cares for Joe until he gets his strength back and then orders Swift Eagle to take Joe into town. In town, Joe meets the most powerful man there, Frank Ryan, who showers Joe with hospitality. Joe feels indebted to both Red Cloud for saving his life, and to Frank Ryan for extending hospitality in an unfamiliar town. So when Red Cloud challenges Frank to a fight to the death, Joe tries desperately to keep the peace. The reason for the fight? Fifteen years ago, Frank took Red Cloud's warbonnet, and has been proudly displaying it ever since, on the wall in his saloon. Red Cloud, now an old man, must regain his honor before he dies.
Neta, a teen-age girl who is a friend of Jamie's, witnesses an assault and robbery. The victim - Mr. Trumbull, a man who is about to inherit a fortune - dies. The culprit, a drifter named Griff Bannon, gets a glimpse of Neta and, after fleeing the scene, plots to assume his victim's identity and stalk the witness. Her father, meanwhile, is no help, since he raises her by ""traditional values"" and forbids her to socialize with the Cartwrights. Meanwhile, the imposter - now working for the Cartwrights - begins to track Neta's every move and plans to seal her silence, unless she can summon the courage to tell Jamie and the others about the crime she witnessed and identify the baddie.
Joe is shot and wounded while he is on a cattle drive in the Nevada desert. Two ranchers find him, delirious from thirst and the heat, and take him to their home to recover. While the ranchers summon a doctor, Joe struggles for life, mumbling incoherently and having surrealistic nightmares about a teepee and a wagon wheel. Ben and Hoss try to dechipher Joe's ramblings to piece together what happened.
Jamie deliberately disobeys Ben's order not to drive the supply wagons. During his recklessness, the wagon goes out of control on a sharp curve and is wrecked. Nobody is hurt but a badly injured horse has to be put to sleep. Fearing punishment, Jamie decides to run away, until Ben decides to take him on a tour of the Ponderosa, namely to see how others handle their mistakes in positive and negative ways.