An acute febrile illness associated with gastrointestinal upset developed in a patient within one week after starting treatment with methyldopa. The illness was characterized by prompt subsidence of symptoms when the patient withdrew therapy secondary to gastrointestinal upset, and recrudescence of symptoms when methyldopa therapy was reinitiated. This was associated with hyperamylasemia, hyperlipasemia, hyperpyrexia, and epigastric pain, both on admission to the hospital and upon rechallenge with methyldopa. Although gastrointestinal upset has been reported as an untoward side effect of methyldopa, this is the first report to our knowledge of documented methyldopa-induced hyperamylasemia and hyperlipasemia secondary to pancreatitis.