Pentavalent antimony (Sbv), formulated as sodium stibogluconate or meglumine antimoniate, is the standard treatment for the leishmaniases. In 16 of 17 consecutive, prospectively observed patients in Washington D.C., serum levels of amylase and lipase rose to abnormal values after therapy with sodium stibogluconate was started; 12 of 17 had symptoms of pancreatitis. Sbv therapy was continued to completion in 7 of 17 patients and interrupted in 10 of 17. Pancreatitis improved in every patient after Sbv therapy was stopped. Sbv treatment was resumed after brief interruptions in 6 of 10 patients. All six of these patients had flares of pancreatitis, but each completed therapy. Subsequently, we measured amylase and lipase levels in stored sera from 32 patients treated in Peru with either sodium stibogluconate or meglumine antimoniate for mucosal leishmaniasis. In all 32 Peruvian patients, serum amylase and lipase rose to abnormal levels during Sbv therapy; 11 of 32 had symptoms of pancreatitis. Standard Sbv regimens induce pancreatitis in almost all patients, but continued therapy is often tolerated; pancreatitis subsides when therapy is stopped, and rechallenge may be tolerated after a brief halt in treatment.