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The scene is San Francisco's Barbary Coast, where missionary Arthur Worden (William Desmond) fights a losing battle to save the souls of the wicked denizens. Taking up residence in a theatrical boarding house, Worden meets cabaret dancer Ferda Maxey (Dorothy Dalton). He instantly falls in love with her, but she spurns him, preferring to join a group of her fellow chorines for a tour of Australia. Coincidentally, Worden is on his way to spread the Word in China, and he books passage on the same ship bearing Ferda and her friends. On cue, the ship is wrecked on the high sea, and Worden and Ferda are washed ashore on a desert island. Manfully resisting temptation, Worden refuses to take advantage of the vulnerable Ferda, declaring his love for her only after saving her from the lecherous advances of a third castaway. Touched by Worden's sincerity, Ferda accepts his marriage proposal and vows to change her ways once she returns to civilization. The highly moral atmosphere of Gamble in Souls was somewhat undercut by the revealing "jungle" costumes worn by leading lady Dorothy Dalton.