Effects of trimebutine maleate (TM-906) on the spontaneous contraction of isolated duodenum and ileum were studied in both guinea pigs and rabbits. In the duodenum and ileum of both guinea pigs and rabbits, TM-906 (10(-6) g/ml, 10(-5) g/ml) produced a potentiation of the spontaneous contraction in preparations with low contractile activity (low tone or small contraction), while it caused an inhibition of the spontaneous contraction in preparations with high contractile activity (high tone or large contraction). The potentiation of spontaneous contraction by TM-906 was more pronounced in the ileum than in the duodenum of both guinea pigs and rabbits. When the spontaneous contraction of duodenum and ileum was decreased by atropine, the potentiation of spontaneous contraction by TM-906 was further augmented and was more pronounced in the ileum than in the duodenum. When the spontaneous contraction was remarkably potentiated by physostigmine or acetylcholine, TM-906 markedly inhibited the potentiated spontaneous contraction, and the potentiation by TM-906 seen in preparations with low contractile activity disappeared. From these results, it is concluded that TM-906 produces, depending on the contractile activity of the preparations, a potentiation or an inhibition of the spontaneous contraction of duodenum and ileum in both guinea pigs and rabbits and that the potentiation by TM-906 is more pronounced in the ileum than in the duodenum. It is suggested that the endogenous acetylcholine partly modifies the effects of TM-906, but that it does not relate to the more pronounced potentiation by TM-906 in the ileum than in the duodenum.