Peptic digestion of gluten results in the production of substances having opiatelike activity in bio- and receptor assays. These substances have been termed exorphins. In this study, we determined the effect of gluten, hydrolyzed gluten, and hydrolyzed gluten plus the opiate blocker naloxone on a variety of hormonal parameters, gastrointestinal transit time, small bowel mucosal integrity, and satiety. Hydrolyzed gluten prolonged intestinal transit time, and this effect was reversed by concomitant administration of naloxone. Hydrolyzed gluten also produced a naloxone-reversible increase in plasma somatostatinlike activity, which may have been responsible for the delayed transit time. No effects of the "exorphins" could be demonstrated on serum gastrin, cortisol, carbohydrate metabolism, or small bowel mucosal integrity. Although a number of studies have suggested a role for endogenous opiates in appetite regulation, we could not demonstrate any effect of "exorphins" on the amount of calories ingested nor on the perception of satiety. This study defines a potential role for small opiatelike peptides in foodstuffs in the regulation of intestinal function.