Short-chain fatty acids (SCFAs) are recognized as the major anions of the large intestinal content in humans, but their effect on colonic motility is controversial. This study explores the colonic motor effect of SCFAs and their mechanisms in the rat. Colonic motility (electromyography) and transit time (plastic markers) were measured in conscious rats while SCFAs were infused into the colon, either alone or after administration of neural antagonists or immunoneutralization of circulating polypeptide YY (PYY). SCFA-induced PYY release was measured by RIA and then simulated by infusing exogenous PYY. Intracolonic infusion of 0.4 mmol/h SCFAs had no effect, whereas 2 mmol/h SCFAs reduced colonic motility (36 +/- 3 vs. 57 +/- 4 spike bursts/h with saline, P < 0.05) by decreasing the ratio of nonpropulsive to propulsive activity. This resulted in an increased transit rate (P < 0.01). Neither alpha-adrenoceptor blockade nor nitric oxide synthase inhibition prevented SCFA-induced motility reduction. Intraluminal procaine infusion suppressed the SCFA effect, indicating that a local neural mechanism was involved. SCFA colonic infusion stimulated PYY release in blood. Immunoneutralization of circulating PYY abolished the effect of SCFAs on colonic motility, whereas exogenous PYY infusion partly reproduced this effect. SCFAs modify colonic motor patterns in the rat and increase transit rate; local nerve fibers and PYY are involved in this effect.