Studies were carried out in 25 healthy male volunteers to investigate the effect of ileal infusion of solutions of different nutrient composition and osmolality on the profiles of a radiolabeled solid meal emptying from the stomach. Ileal infusion of a 50% corn oil emulsion or a 20% oleic acid emulsion slowed the rate of gastric emptying compared with ileal infusion of isotonic saline (0.9%). In contrast, infusion of either hypertonic saline (430 mosmol), distilled water, or isotonic solutions containing protein hydrolysate (8 g%) or glucose (50 mM) had no effect on the gastric emptying profile. These experiments support the hypothesis that the presence of unabsorbed lipid or fatty acids in the distal small intestine may delay gastric emptying, but suggest that sugars and proteins are ineffective. As infusion of both protein hydrolysates and lipid into the ileum can delay small bowel transit in humans, the data suggest that ileal regulation of gastric emptying and small bowel transit may be mediated by different mechanisms.