The actions of cisapride on electrical behavior of single myenteric neurons and on the propulsive activity of segments of ileum were studied in vitro. Cisapride (10-300 nM) did not affect the membrane potential, resting properties, or active properties of S neurons. The amplitude of fast nicotinic excitatory postsynaptic potentials recorded from S cells was increased by cisapride in the concentration range of 10 nM to 1 microM. Higher cisapride concentrations (3-10 microM) reduced the amplitude of fast excitatory postsynaptic potentials. Potentiation of fast excitatory postsynaptic potentials by cisapride was antagonized by ICS 205-930 (1 microM) but was unaffected by GR 38032F (1 microM), both compounds being 5-HT3-receptor antagonists. Cisapride did not modify the electrical behavior of AH neurons except at the highest concentrations (3-10 microM), which caused hyperpolarization of some neurons. The propulsive efficiency (i.e., number of peristalses and total amount of fluid ejected per unit of time) of isolated segments of ileum was enhanced by cisapride (100 nM to 3 microM). Higher cisapride concentrations (6 or 10 microM) had a depressant action on propulsive activity. The stimulatory effect of cisapride on propulsion was not antagonized by ICS 205-930 (300 nM or 1 microM). These data indicate that cisapride facilitates cholinergic transmission in the myenteric plexus of guinea pig ileum and that this effect may be at least partially responsible for the increased propulsive efficiency observed in ileal segments.