Based on earlier observations that colonic contents stimulated ileal motility in the dog, our hypothesis is that the ileum would respond to physiological amounts of short-chain fatty acids (SCFA). Four dogs had isolated ileocolonic loops constructed surgically and boluses of test solutions (15 ml) were instilled into the distal ileum through a small catheter. Intraluminal pressure catheters were used to record motility. Concentrations of SCFA (also called volatile fatty acids) comparable to those found in dog stool (108 mM; 66% acetic, 24% propionic, and 10% butyric acids) regularly stimulated motility with a dose-related effect. The response was not due to the pH of the SCFA solutions and was independent of the pH at which SCFA were instilled. Ricinoleic acid (4 mM) also stimulated motility, as did chenodeoxycholic acid; the bile acid was active only at supraphysiological concentrations (approximately 7.6 mM). Instillates that simulated the composition of ileal chyme in malabsorptive states were without effect. The results suggest that the ileum can "sense" the presence of colonic contents in the lumen and that SCFA are the responsible mechanisms. Stimulation of ileal motility by SCFA could be a response to coloileal reflux.