AbstractThe effect of serotonin (5‐HT) and of more selective 5‐HT agonists on the peristaltic reflex evoked in the isolated guinea‐pig ileum was investigated. Using the Trendelenburg technique, peristaltic contractions were elicited by increasing intraluminal pressure, and rhythmic contractions of the longitudinal and circular muscle were measured after serosal administration of the drugs. 5‐HT potently stimulated contractions of the longitudinal muscle. The effect of 5‐HT was partly antagonized by the 5‐HT4receptor antagonist SDZ 205–557. Of the potent 5‐HT1Areceptor agonists, 8‐OH‐DPAT, 5‐carboxamidotryptamine (5‐CT) and dipropyl‐5‐CT (DP‐5‐CT), only 5‐CT caused a substantial stimulation. Of the 5‐HT1C‐/5‐HT2receptor agonists DOI and 5‐methoxytryptamine (5‐MeOT), DOI was inactive, whereas 5‐MeOT potently stimulated contractions. 5‐HT1Dreceptor agonists (5‐CT1sumatriptan) had a stimulatory effect. The effect of sumatriptan was antagonized by the 5‐HT1Dreceptor antagonist metitepine but not by the 5‐HT4receptor antagonist SDZ 205–557. The 5‐HT3receptor agonist 2‐methyl‐5‐HT and the antagonists ICS 205–930 and granisetron did not influence the peristaltic reflex. 6‐OH‐indalpine, a 5‐HT1Pagonist, was inactive. This data suggest that 5‐HT stimulates the peristaltic reflex in the isolated guinea‐pig ileum by activation of 5‐HT4‐ and 5‐HT1Dreceptors; other 5‐HT recep