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In 1866, on the island of Hawaii, the United States government decrees that all lepers must report for deportation to a settlement on the island of Molokai. When one of the notices is posted on the door of Father Joseph Damien de Veuster's rectory, the priest tears down the sign, distressed because several of his ailing parishioners are to be exiled to Molokai. As Damien attempts to comfort the exiles, a trooper interrupts him with news that one of his parishioners, Keaka, has attacked a guard and taken refuge in the hills with his leper wife. Following Keaka into the hills, Damien assures him that he may accompany his wife to Molokai, and Keaka chooses to join his wife in her journey to the "island of the dead." Seven years later, Damien is summoned by the bishop to assist in the dedication of a new church on the island of Maui. After the ceremony, the bishop appeals for a volunteer to go to the leper settlement, and Damien pleads to be the one chosen. Soon after, Damien arrives on Molokai and is met by three men carrying a corpse and a furious old man pelting him with stones. In terror, Damien runs to the little chapel standing alone by the sea under the cliffs. Bursting through the door, Damien collapses at the alter when the figure of a man turns to embrace him. Fearful at first, Damien recognizes the man as Keaka, welcoming him to the island. Behind them, three people shyly come forward to meet the priest: Milo, a young girl whose mother is dying of leprosy, and Amalu and Pua, who have accompanied their ailing relatives to the island. In Honolulu, meanwhile, the Board of Health convenes to allot funds for the leper colony. Although the Board is supportive, budget constraints dictate that only thirty-five dollars for lumber may be apportioned. On Molokai, the lumber is shaped into coffins for victims of the disease. When a Hawaiian family refuses a Christian burial for their child, Damien, despairing that he will not be able to establish a Christian congregation, returns defeated to the chapel and tells his four healthy friends that they must leave the island. In unison, they insist on staying with their beloved priest. Soon after, Kamuela, a recent arrival, storms into the chapel and spits on Damien's extended hand of greeting. Kamuela, a young leper from the city, charges that he has been refused shelter because he is a Protestant. In a heated exchange, Kamuela takes a pipe from the priest's pocket, places it in his mouth and then dares the priest to smoke it. When Damien lights up the pipe and invites Kamuela to spend the night in the chapel, he and the young leper become friends. Desperate for supplies, Damien travels to Honolulu, violating a law that forbids the inhabitants of the colony to leave the island. Damien's pleas to the Board of Heath move the members to empty their own pockets to provide supplies for the leper colony. With these funds, Damien buys lumber, tools and pipe to build a system to supply water to the waterless settlement. On Molokai, the lepers who have been won over by Damien's dedication, load the supplies into wagons and begin to build the pipeline and new housing. On Damien's birthday, the pipeline is finally completed. As the visiting members from the Board of Health turn the spigot, water splashes and gushes out, and Keaka fills several pitchers with water to take to the priest's new house. On the porch, Keaka notices that Milo is in tears, but when he approaches her, she runs away. After the visitors depart, Damien searches for Milo and finds her in a crumbling old shack. There she confides that she has fallen victim to the dreaded disease. Some time later, Princess Liliuokalani, the Regent of Hawaii, visits the settlement. Milo, ravaged by the disease, is now unable to walk or stand, and Kamuela is bandaged to his neck. Side by side, the princess and the priest walk to meet the inhabitants of the colony. Twelve years after Damien's arrival on the island, Kamuela rumages through the priest's desk to find the Princess' letter bestowing the order of Kalakawa on Father Damien. When Damien snaps at Kamuela, Kamuela hobbles on his crutches out of the house, weeping. Bitter and angry that his appeals for aid have fallen on deaf ears, Damien himself now has fallen victim to the disease. When Keaka implores him to seek treatment in Honolulu, Damien refuses, claiming that his work is his life. Damien then extends his hand to Keaka, and together, they return to their labors.