Leptospirosis, severe infection due to Leptospira interrogans, is a potentially lethal disease that causes multiple organ failure. In addition to hepatic, renal, and CNS involvement, which are classic complications of leptospirosis, the disease may also be complicated by adult respiratory distress syndrome. Treatment with penicillin may precipitate a severe Jarisch-Herxheimer reaction. The mechanisms of Leptospira-induced toxicity remain obscure. We report a near-fatal case of leptospirosis in a patient who developed a JHR and respiratory failure immediately after initiation of therapy.