Six-year-old Jenny (Natalie Wood) rescues a collie dog, the only survivor of a plane wreck. A tag on the dog's neck states that it is en route to a medical laboratory where its blood will be used for spotted fever vaccine. Dr. Steven Webster (Dean Jagger) meets both Jenny and the dog and "adopts" them both. His fiancee Susan (Ruth Warrick) isn't too fond of either the girl or the dog. Webster wants to get a hospital for the town but he is suppressed by the town mayor (Jerome Cowan.) In the arguments that follow, Webster's lab is wrecked and ticks infected with spotted fever escape. The town is in a panic and all want to be vaccinated. Jenny is infected and is about to die.

At a church in Bullfrog Springs, Nevada, young Jenny Hollingsworth weeps as her grandfather and sole guardian, a frail country reverend, dies of old age. When night falls, a plane from the nearby flight academy crashes, and a collie that was traveling on the plane befriends Jenny. When Dr. Steve Webster discovers Jenny with the dog, which she has named "Hollingsworth," he decides to take her to Sheriff Bolton. The sheriff asks Steve to look after Jenny until arrangements can be made for her to stay with another reverend. At Steve's house, Jenny hides an identification card which she found near the crash site. Later, as Murph, the local pharmacist, gives Jenny a bath, he tells her that Susan's aunt Mathilda has waited thirty years for her lover, Wilbur Brown, to return. The sheriff calls to say that the reverend who was to take her in has also died, so Steve decides to leave Jenny with his sweetheart, a schoolteacher named Susan Moore. At Susan's house, Steve becomes jealous of Mayor Snyder, who, she says, wants to marry her. Despite his feelings, Steve tells Susan that he will leave for a position at the Field Institute in San Francisco as soon as he receives his acceptance letter. When Jenny meets Mathilda, she inadvertently upsets her when she repeats what Murph has told her about Wilbur. Steve takes Jenny to Judge Beckett, who is also a tailor, and offers tonsillectomies for all three of his sons in exchange for one dress for Jenny. When Mathilda complains to Murph about his comment to Jenny, he explains that he meant he had been waiting thirty years for her. Outside Steve's house, the mayor's son Lester teases Jenny, and Hollingsworth lunges at him. Later, at his home, Steve prepares to vaccinate Jenny against Rocky Mountain spotted fever when he is distracted by the mayor, who has come to complain about the attack on his son. Soon after, Steve's acceptance letter arrives, and Jenny hides it, afraid that he will leave her. When the sheriff comes to take Hollingsworth, Jenny sets the dog free, and is bitten by one of Steve's experimental, infected ticks. The mayor decides to prosecute Hollingsworth for allegedly biting his son, and the judge rules to have the dog destroyed, but when Murph examines the boy, he fails to find a bite mark. Back at Steve's, Jenny shows him the identification card she has hidden. Later, when Clem Perkins' son Blaine contracts spotted fever, the whole town lines up for vaccinations. Meanwhile, Jenny breaks into the jail and frees Hollingsworth. When Steve learns that the downed academy plane had been carrying a dog to be used in experiments conducted by Dr. Nicholas Adams, he realizes that the dog is Hollingsworth. After Jenny falls ill, Steve contacts Dr. Adams, who is also working on a cure for spotted fever. Dr. Adams explains how to make a serum using the dog's blood, which saves Jenny's life. When the Institute learns about the serum, Steve receives a $5,000 grant to continue his research, but decides to stay to rear Jenny with Susan.