We studied the effect of Y-25130 on the intestinal fluid secretion induced by 5-HT and cholera toxin in rats. 1) Net fluid secretion was increased dose-dependently by intramesenteric artery infusion of 5-HT (1-10 micrograms/min). 2) Y-25130 (0.01-1 mg/kg, iv) inhibited the net fluid secretion induced by 5-HT (3 micrograms/min). Granisetron and ondansetron also inhibited the net fluid secretion induced by 5-HT. 3) Methysergide did not inhibit the fluid secretion, and neither atropine nor tetrodotoxin inhibited it. 4) Cholera toxin (1-10 micrograms/2 ml into jejunal loops) caused profuse net fluid secretion. 5) Y-25130 (1 mg/kg, iv) inhibited the net fluid secretion induced by cholera toxin (3 micrograms/2 ml). Granisetron was inhibitory and ondansetron tended to inhibit the cholera toxin-induced secretion. These results suggest that 5-HT may increase the net fluid secretion through 5-HT3 receptors, and cholera toxin-induced fluid secretion may be at least partially mediated by 5-HT3 receptors. It is expected that Y-25130 may be useful for treating secretory diarrhea in humans.