The newly recognized class of 5-hydroxytryptamine receptors (5HT₃) may be involved in the induction of nausea, since their pharmacological antagonists are effective against emesis induced by chemotherapy. 5HT₃ receptors are present on enteric neurons, and 5HT₃ blockers may produce mild constipation; we thus hypothesized that 5HT₃ receptors would modulate colonic motility. To determine if GR 38032F, a selective 5HT₃ antagonist known to have antiemetic effects, influences colonic transit in health, a randomized, double-blind, placebo-controlled crossover study was performed. Using a radiopaque marker technique, colonic transit was quantified in 39 healthy volunteers (19 men, 20 nonpregnant women) 18–70 years of age. On a standard 25-g fiber diet, 16 mg of GR 38032F was given orally thrice daily. Gastrointestinal peptides (peptide YY, human pancreatic polypeptide, neurotensin, motilin, gastrin-cholecystokinin, substance P) were also measured in plasma fasting and postprandially. Mean total colonic transit time on placebo was 27.8 hr, while on GR 38032F it was 39.1 hr (P<0.0005). transit="" times="" through="" the="" left="" colon=""><0.0005) and="" rectosigmoid=""><0.05) were="" prolonged="" by="" the="" drug,="" but="" right="" colonic="" transit="" was="" not="" significantly="" altered.="" transit="" times="" did="" not="" correlate="" with="" age="" or="" gender,="" but="" subjects="" with="" shorter="" transit="" times="" were="" significantly="" more="" affected="" than="" were="" those="" with="" longer="" transit="" times.="" the="" peak="" release="" of="" peptide="" yy="" was="" minimally="" decreased="" following="" gr="" 38032f=""><0.01), but="" the="" peak="" and="" integrated="" postprandial="" responses="" of="" human="" pancreatic="" polypeptide,="" neurotensin,="" motilin,="" gastrin-cholecystokinin,="" and="" substance="" p="" were="" not="" significantly="" altered="" by="" the="" drug.="" we="" conclude="" that="">₃ receptors may be involved in the regulation of colonic transit in healthy man.