A leptospirosis surveillance program was carried out for 12 months on the entire population of the Seychelles. Diagnosis was assessed by both microagglutination test and polymerase chain reaction (PCR) assay. In this population of 74,331, leptospirosis was clinically suspected in 125 subjects and confirmed in 75 patients (incidence of 101 per 100,000; 95% confidence interval = 79-126). Leptospirosis was more frequent in middle-aged males with environmental exposure. Eight serogroups were identified and Icterohaemorrhagiae (31%) and Hurstbridge (20%) were the most frequent. Hurstbridge, a recently identified new serogroup, was implicated in severe cases and death. Influenza-like forms accounted for 37% of the cases while jaundice, acute renal failure, and pulmonary hemorrhage occurred in 52%, 28%, and 19%, respectively. Death occurred in six patients and was related to pulmonary hemorrhage. The PCR result was positive after completion of treatment in eight patients, suggesting that the administered five-day course of penicillin may be inadequate to eradicate the bacteria.