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Recent controlled clinical trials have documented the development of acute pancreatitis in 5% of patients receiving azathioprine for Crohn's disease, by far the highest incidence of drug-induced pancreatitis recorded to date. In an effort to evaluate the effects of azathioprine on the pancreas, the isolated ex vivo perfused canine pancreas model was used. No significant changes in gross appearance, weight, or serum amylase occurred in azathioprine-treated glands compared to controls. Azathioprine administration, however, resulted in a significant increase in secretory volume (two fold) and bicarbonate output (two fold), and a profound depression of trypsin output compared to controls. These preliminary studies demonstrate that azathioprine has marked effect on pancreatic function in this model.