Between 1967 and 1987 in the Southern Marquesas, a remote archipelago in French Polynesia, the detection rate of leprosy was 48.9 per 100,000 when it was 8.6 per 100,000 for French Polynesia as a whole. In 1988, a program of chemoprophylaxis of leprosy with a single dose of 25 mg/kg rifampin was implemented, and 2751 persons (98.7% of the population) were treated in the Southern Marquesas. In addition, 678 South Marquesans and 2466 members of their families living in the Northern Marquesas and in the Society Archipelago, received the same chemoprophylaxis. Among 2676 persons studied in the Southern Marquesas (97.4% of the treated population), 130 had elevated IgM anti-phenolic glycolipid-I antibodies by ELISA without any evidence of leprosy. The onset of a skin lesion of borderline leprosy in a boy 3 months after chemoprophylaxis raises the question of the nature of such a skin lesion and, indirectly, of the effectiveness of the chemoprophylaxis.