Chronic reserpine treatment (500 micrograms/kg) of the rat results in generalized exocrinopathy, impaired pancreatic secretion, and decreased pancreatic amylase. These characteristics are similar to those in cystic fibrosis and are the basis for use of this experimental model for cystic fibrosis. Pancreatic enzymes adapt to diet, but it is not known whether chronic reserpine treatment affects this response. Due to the malnutrition induced by this treatment, another dose of reserpine was required that would alter pancreatic function but not induce malnutrition in order to evaluate dietary adaptation. Male rats (100-120 g) were injected subcutaneously daily for 7 days with 1) no injection (control); 2) 1.0 ml/kg vehicle or sham (pair fed-sham); or 3) reserpine: 500, 50, or 5 micrograms/kg. Food consumption was comparable among control and reserpine-treated (50 and 5 micrograms/kg) rats and significantly greater (200%) than pair fed-sham and 500 micrograms/kg reserpine-treated rats. Pancreatic amylase, however, was significantly lower in all reserpine-treated rats (500 micrograms/kg, 74%; 50 micrograms/kg, 56%; 5 micrograms/kg, 52%) than in control rats. To evaluate dietary adaptation, control and reserpine-treated (5 micrograms/kg) rats were fed high carbohydrate, high fat or high protein diets. Both groups adapted to these diets with the greatest amylase, lipase, and trypsin activities in high carbohydrate-, high fat-, and high protein-fed rats, respectively. Reserpine-treated rats fed high carbohydrate, however, had significantly lower (64%) amylase activity than high carbohydrate-fed control rats. Although reserpine-treated rats can adapt pancreatic enzymes to diet, the adaptation of amylase to carbohydrate is impaired.