A stray dog brings together a young boy and an old man in the Georgia swamps.

In Mississippi swamp country, kindly Jesse Jackson is rearing his orphaned nephew Claude, whom he has nicknamed Skeeter. Although the toothless, illiterate older man cannot teach him what is taught at school, he lets Skeeter practice reading to him and shows him the right way to live in harmony with nature. During a moon-filled night, Skeeter hears a strange sound and wakes Jesse. He tells Jesse the sound was "like a ghost laughing." As uncle and nephew leave their weather-beaten cabin to find the source of the sound, Skeeter chatters away about his desire to own a .22 gauge shotgun for hunting. Soon they encounter a creature that looks like a dog, licks itself like a cat and does not bark, but makes a laughing sound. Unlike other creatures, the animal can smell them from a great distance and shyly runs away from them. The next day, their friend, storekeeper "Cash" Evans, drops by with groceries. After hearing about the creature, he lets his hunting dog and hog hounds loose, and he and the Jacksons follow them. They determine that the creature is a dog, and when she outruns and outsmarts Cash's highly trained dogs, the storekeeper is amazed. Later, sensing that the dog wants him as much as he wants her, Skeeter patiently lures her with food. The little dog's eyes are filled with tears when Skeeter gets near her and takes her home. Skeeter and the dog, which he names "Lady," become inseparable. Lady sleeps with Skeeter and eats the same meager meals as the Jacksons. At mealtime, remembering the taste of hickory nuts, Jesse talks about buying "Roebuckers," which is his name for false teeth from the Sears Roebuck catalog. Fearing that Lady could be harmed by the alligators in the swamp, Skeeter sternly trains Lady to go against her instincts and chase birds, instead of swamp rats. One of Skeeter's chores is to get buttermilk from Bonnie Dew and her oldest son Gates, African-Americans who live across the river. Bonnie Dew is shocked to learn that Jesse lets Skeeter drink coffee, even though Jesse always adds a little milk. Gates, a perceptive man, asks Skeeter what is bothering him and assures him that dogs can be taught to do anything but laugh and cry. After several months of training Skeeter, Lady surpasses the hunting skills of Cash's new English setter, Millard Fillmore. News travels that Lady can run faster than other hunting dogs and smell prey over fifty yards away, bringing whole families to the backwoods cabin to see her. One day while Skeeter is out, Cash visits Jesse reluctantly to tell him about a lost-and-found ad he read in a magazine, reporting that a rare African hunting dog, called a Basenji, was lost in their area. The lost dog, named "Isis of the Blue Nile," fits Lady's description. Cash suggests not telling Skeeter about Lady's rightful owner, who lives in Connecticut, but Jesse feels a moral obligation to tell Skeeter the truth. That evening, when Jesse tells Skeeter, the boy tries to deny that Lady is the dog described in the ad and Jesse promises to respect his decision. However, after some thought, Skeeter announces that he must contact the owner. Unsure of the best way to reach the owner, Skeeter consults Gates, who admits to seeing the ad and offers to send a telegram on Skeeter's behalf. Almost in tears, Skeeter demands to know why Gates never mentioned the ad earlier, when parting with the dog would have been easier for him. Gates says that he tried to catch the dog himself for the reward, but the dog chose to be with Skeeter and he could see how Skeeter "ached" for the dog. Later, in response to the telegram, Walden Grover, an employee of the kennel that owns Lady, comes to the cabin to retrieve her. While waiting for Skeeter and Lady to return from the woods, Grover and Jesse behave with stiff politeness, until Jesse, admitting that they are both "a bit touchy," invites him into the cabin. Grover confides his discomfort about separating the boy from the beloved, but rare and expensive dog. When Skeeter is late coming home, Grover goes to Cash's store to wait. Later Skeeter, Jesse and Lady arrive, and Skeeter apologizes for his tardiness. Instead of the fifty dollar reward promised in the ad, Grover gives Skeeter one hundred dollars for the return of Lady. When Cash suggests that Skeeter could buy one of Lady's litter, Skeeter says that the puppy would remind him of Lady and prolong his grieving. Hearing this, Grover promises not to write him to report how Lady is doing. Because Lady refuses to obey Grover's order to go to the car, Grover asks Skeeter to carry her there. At first Skeeter refuses, feeling that he has done enough, but then agrees, admitting that Grover paid him fairly. After putting the crying dog in the carrier in the back of Grover's truck, Skeeter says "good-bye, my Lady," and Grover drives away. Cash consoles Skeeter that Lady will be well cared for and asks him to train Millard Fillmore. Jesse expects Skeeter to decline the offer, but, to his surprise, Skeeter agrees that "Old Mill" barks like the kind of dog he is used to, and adds that Lady will be better off eating meat every day. With his money, Skeeter insists that he will buy Jesse the best set of false teeth in the Sears Roebuck catalog and asks Cash to place an order. Cash suggests that there will be enough money left to make a down payment on a shotgun. Skeeter brightens, momentarily forgetting that Lady will not be there to hunt with him, but decides to go ahead with the plans. Cash offers them coffee and Jesse, observing that Skeeter is growing up, serves him his coffee black.