The secretion of gastric acid in normal and streptozotocin-induced diabetic rats was studied. Female rats were injected with streptozotocin (64 mg/kg BW, iv) or vehicle. Three days later, all rats were fasted overnight before anesthetization with pentobarbital (25 mg/kg BW, ip). The right jugular vein was catheterized. A PE-160 tubing was inserted into the esophagus and ligated at cervical level. A PE-320 cannula was introduced into the stomach through an incision in the duodenum and was ligated about 0.5 cm from the pylorus. The stomach was flushed through the esophagus cannula via a peristaltic pump with 10 ml saline at room temperature and then irrigated with saline. Acid output was determined by titration of the flushed perfusate with 0.01 N NaOH to pH 7.0. Basal secretions were collected for 45 min before infusion of pentagastrin (8 micrograms/ml/300 g BW) for 30 min, then for an additional 75 min. Blood samples were collected via jugular catheter at 0 min and 150 min following acid collection. Pentagastrin infusion stimulated gastric acid secretion in both diabetic and normal rats. The spontaneous gastric acid secretion in diabetic rats was not significantly different from that in normal animals. However, the secretion of gastric acid in response to pentagastrin was greater (p less than 0.05 to p less than 0.01) at 20, 30, and 35 min following pentagastrin infusion in diabetic rats than in normal females. Pentagastrin infusion stimulated gastric inhibitory polypeptide (GIP) secretion by 1.8-fold (p less than 0.05) in normal but not diabetic rats. The basal level of plasma GIP was higher (p less than 0.05) in diabetic than in normal rats. These results suggest that the increase of pentagastrin-induced gastric acid output in STZ-diabetic rats compared with normal controls is independent of GIP secretion.