Studies were carried out in 7 healthy male volunteers to investigate whether the delay in small bowel transit time, induced by the infusion of fat emulsions into the human ileum, was mediated by endogenous opioids. The effect of ileal infusion of intralipid on small bowel transit time of a 100-ml solution containing 13.3 g of lactulose was studied during intravenous infusion of either saline or naloxone (20 micrograms/kg X h) in saline. During intravenous infusion of saline, ileal infusion of fat significantly delayed small bowel transit time of the head of the lactulose infusion (ileal intralipid vs. saline; 249 +/- 46 vs. 44 +/- 8 min; mean +/- SEM; p less than 0.01). Intravenous infusion of naloxone, however, abolished the delay in small bowel transit time induced by ileal infusion of intralipid in 5 of 7 subjects (intravenous naloxone; ileal intralipid vs. saline; 89 +/- 26 vs. 46 +/- 8 min; p greater than 0.2). Intravenous naloxone had no effect on small bowel transit time when saline was infused into the ileum. This result suggests that endogenous opioids may be involved in the feedback regulation of small bowel transit by ileal intralipid.