The effects of trimebutine on the electrical properties of smooth muscle membranes were studied in the isolated rat stomach, the objective being to elucidate the dual actions of this drug on gastric motility. Transmural nerve stimulation elicited a cholinergic excitatory junction potential (e.j.p.) and a nonadrenergic noncholinergic inhibitory junction potential (i.j.p.), and trimebutine inhibited the e.j.p. more than the i.j.p., with no significant change in the acetylcholine-induced depolarization. Trimebutine reduced the interval and, at high concentrations, the amplitude of slow waves. In enzymatically dispersed single cells, the Ca2+ current elicited by depolarization of the membrane was also inhibited by trimebutine. Thus, trimebutine increases slow wave frequency and inhibits cholinergic transmission and Ca2+ influx. The former would enhance while the latter two would depress gastric motility.