The possibility that 5-hydroxytryptamine (serotonin; 5-HT) mediates bowel dysfunction caused by stress was evaluated in rats and mice treated with 5-HT or thyrotropin-releasing hormone (TRH) injection and in rats subjected to stress. Restraint stress at room temperature (23 degrees C) significantly increased fecal pellet output without the formation of gastrointestinal mucosal lesions in free-feeding rats, and caused diarrhea in 90 to 100% of animals within 3 hr in food-deprived rats. Oral YM060, ondansetron, granisetron, atropine and diazepam and s.c. tetrodotoxin inhibited these stress-induced changes in bowel function in fed and fasted rats. ED50 values were 1.1 (0.2-6.6) and 2.5 (1.1-5.7) micrograms/kg for YM060, 483 (338-691) and 354 (262-477) micrograms/kg for ondansetron, 208 (111-393) and 142 (48.9-414) micrograms/kg for granisetron, 811 (639-1,030) and 847 (641-1,118) micrograms/kg for atropine, 3,099 (1,499-6,405) and 5,396 (4,768-6,106) micrograms/kg for diazepam and 1.9 (1.7-2.1) and 3.3 (1.6-6.5) micrograms/kg for tetrodotoxin, respectively. Methysergide inhibited stress-induced diarrhea with an ED50 value of 724 (384-1,366) micrograms/kg s.c., whereas it had partial effect on stress-induced increases in fecal pellet output. Exogenous 5-HT increased fecal pellet output in rats and caused diarrhea in mice.(ABSTRACT TRUNCATED AT 250 WORDS)