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In 1907, hunter John "Lonni" Douglas, who has spent his life in the Belgian Congo struggling to earn money, is irritated by the arrival of Ellen Burton, a beautiful nurse who has come to the Congo to work with missionary doctor Mary. The cynical Lonni is suspicious of Ellen's motives for coming to Africa, while Ellen is annoyed by Lonni's male chauvinism. Although Lonni warns Ellen that Dr. Mary has traveled up the Congo River to help the victims of a fever epidemic, Ellen is determined to join her. That evening, fed up with capturing animals for zoos, Lonni tells his Dutch business partner, Huysman, that he is quitting. Huysman, who has spent seven years searching for gold, urges Lonni to remain and shows him a necklace made of gold nuggets, which supposedly came from the region where Dr. Mary is currently working. Huysman states that by escorting Ellen to Mary, Lonni will have a "passport" into the area, although Lonni is worried about traveling so close to the homeland of the mysterious and violent Bakuba tribe. Lonni decides to go, however, and is accompanied by his loyal gun bearer Jacques. When the group reaches a stretch of rapids, they leave the water to travel overland. They stop at a nearby village where a witch doctor is treating the local chief's wife, and when Ellen learns that the witch doctor wants to kill the woman because he believes that she is possessed by evil spirits, Ellen insists on examining her. The chief agrees, and Ellen saves the woman's life by pulling a tooth that has abcessed and infected her lymph nodes. During a feast afterward, Ellen is disturbed by the witch doctor's animosity toward her, and later that night, he attempts to kill her by slipping a tarantula into her tent, but her screams bring Lonni rushing in to save her. Lonni caustically advises Ellen to return home, but Ellen stubbornly insists on persevering. Continuing up river, the group reaches the outpost and learns that Dr. Mary has died from fever. Lonni again believes that Ellen will turn back, but after she successfully delivers a baby, she declares that she will remain at the makeshift hospital. While Lonni grudingly is showing Ellen how to hunt, they see a teenaged Bakuba, Mekope, attempting to complete a warrior rite of passage by killing a lion, but the lion mauls him and Lonni shoots it. Ellen tends to the boy's injuries and assures Lonni that as long as his wounds do not become infected, he will recover. Lonni, who discovered another gold nugget necklace while rescuing Mekope, frets over what to do, and tells Ellen that he will escort the boy home, but does not inform her of his real motives. That evening, however, Lonni confesses to Ellen that his life is empty. Ellen, who had earlier told Lonni that she is a widow, reveals that her doctor husband's dream had been to come to Africa, where he felt he was most needed. Unable to resist his growing attraction to Ellen, Lonni kisses her, but she tells him that she cannot reciprocate, and he accuses her of wanting to share her world with a dead man. When Ellen returns to the compound, she discovers that Mekope is running a fever, but her ministrations are interrupted by the appearance of some Bakuba warriors, who snatch the youth and take him home. The next morning, Huysman, who had heard about Mekope's injuries, arrives and is delighted that Lonni will be able to enter Bakuba territory unmolested when he takes the youth home. Lonni explains that Mekope is gone, however, and Huysman shows him an arsenal of guns and dynamite that he intends to use against the warriors. Just then, they hear a drum message from the Bakubas, summoning Ellen to help Mekope. Hoping to avoid bloodshed, Lonni persuades Huysman to wait while he escorts Ellen to the Bakuba village, then scouts for gold. Ellen is touched by Lonni's willingness to accompany her, although when they arrive, the Bakubas treat Lonni with suspicion. They accept his explanation that "the white witch doctor" needed a guide, and Ellen then sees her patient. Ellen is horrified to learn that Mekope has developed gangrene, but with Lonni's help, sets up a drip to keep medicine flowing over the wound. Impressed by Ellen's devotion, the Bakuba king, who is Mekope's father, tells her that she is the first white person to come to his country to help his people, rather than to rob them. After the king leaves, Ellen tearfully explains to Lonni that she does not deserve his kind words. Ellen relates that when her husband told her his dream of coming to Africa, she talked him out of it, as she did not want to give up her comfortable life, and when he died, she realized she had deprived him of his greatest aspiration. Although Ellen had come to the Congo to make amends, she now realizes that she wants to help others rather than herself, and Lonni is impressed by her transformation. As they talk, a Bakuba killed by a bullet is brought in, and Lonni realizes that the impatient Huysman and his cohorts must be nearby. Lonni confesses to Ellen that he has been using her in his attempts to find gold, but then bravely tells the king that he will go to Huysman and order him to leave. The king insists on keeping Ellen as a hostage, and after she kisses Lonni goodbye, he finds Huysman's camp. Although Lonni declares that there is no gold in the area, one of Huysman's men knocks him out and ties him up. Huysman threatens to shoot Lonni if he does not reveal the truth, but Jacques, who has followed Lonni, sets off the dynamite as a distraction. With Jacques's help, Lonni defeats his enemies, although Jacques is killed during the melee. Lonni returns to the village, where an exhausted Ellen accidentally breaks the novocaine drip. Fortunately, her treatment has proven effective, and Mekope regains consciousness. Later, during a celebration, the king dubs Ellen "Big Mama," as Dr. Mary was called, and overwhelmed with happiness, she embraces Lonni.