Recently, peptides with opioid-like activity have been demonstrated in peptic digests of dietary protein. The present study was designed to determine the effect of digested and undigested gluten on postprandial insulin and glucagon levels in conscious dogs. The intragastric instillation of digested gluten (25 g) elicited a more rapid and a significantly greater rise in postprandial peripheral vein insulin and glucagon levels compared with the effect of 25 g undigested gluten. The incremental insulin level was 104 ± 20 μU/ml after digested gluten and only 58 ± 7 μU/ml (P < 0.01) after undigested gluten; the respective values for glucagon are 426 ± 25 pg/ml versus 302 ± 20 pg/ml (P < 0.01). The intragastric administration of naloxone (4 mg), a specific opiate receptor antagonist, reduced the insulin response and augmented the glucagon response to the digested gluten test meal, whereas the response of both hormones to the undigested gluten meal was not affected by naloxone. Intravenously infused naloxone during the digested gluten meal did not influence insulin or glucagon levels. The present data suggest that in dogs the peptic digest of gluten contains an opioid-like material that stimulates postprandial insulin and glucagon release.