A 23-year-old man experiencing three episodes of acute pancreatitis of undetermined etiology is described. Repeated questioning revealed that all three events had occurred after intake of the drug pyritinol. Controlled rechallenge with a single dose of the drug led to a fourth episode of acute pancreatitis. Skin testing was negative, but lymphocyte stimulation tests and double fluorescence analysis detected pyritinol-activated CD4 and CD8 lymphocytes. Together with the clinical observation that the intervals between drug intake and start of symptoms of acute pancreatitis became shorter with repeated exposure, the data are consistent with an immune-mediated origin of the pancreatitis. Pyritinol has to be added to the list of drugs capable of inducing acute pancreatitis.