We studied gastric inhibitory peptide (GIP) in response to a mixed meal in both adult-onset diabetics and normal controls. The adult-onset diabetic group was also studied for immunoreactive GIP (IR-GIP), insulin, and glucose with a test meal before and after tolazamide therapy. Mean basal and meal-stimulated IR-GIP concentrations were greater (P less than 0.05) in the adult-onset diabetic group than in normal controls. With treatment, mean fasting glucose significantly decreased (P less than 0.05) from 206 +/- 14 to 162 +/- 11 mg/dl, and postprandial glucose concentrations were reduced (P less than 0.05) between 5-180 min. In contrast, after 1 month of treatment with tolazamide, IR-GIP concentrations were not significantly altered. Further, basal and postmeal serum insulin levels were significantly higher (P less than 0.05) after tolazamide therapy. We conclude that the enteroinsular axis in terms of IR-GIP is overactive in adult-onset diabetics; tolazamide therapy does not appear to effect its meal-stimulated response.