The effects of trimebutine (2-dimethylamino-2-phenylbutyl-3, 4, 5-trimethoxy benzoate hydrogen maleate) and metoclopramide (N-diethylaminoethyl-2-methoxy-4-amino-5-chlorobenzamide) on propulsive activity of the isolated segmental colon, and on longitudinal and circular muscle layers of colon in guinea-pig were investigated. Trimebutine in doses up to 10(-7) g/ml slightly stimulated propulsive activity, but in doses as high as 10(-7) g/ml inhibited it. However, metoclopramide (10(-7)-10(-5) g/ml) stimulated propulsive activity in a dose dependent manner. Neostigmine-stimulated propulsive activity was inhibited by trimebutine (10(-6) g/ml) but potentiated by metoclopramide (10(-5) g/ml). Trimebutine (10(-8)-10(-5) g/ml) contracted circular muscle layer in a dose dependent manner, and contracted longitudinal muscle layer in doses up to 10(-7) g/ml, but in doses as high as 10(-7) g/ml relaxed it. While, metoclopramide (10(-8)-10(-5) g/ml) contracted both muscle layers. These results indicate that, at high doses, trimebutine-induced inhibition of propulsive activity may depend on a relaxation of longitudinal muscle, and at low doses, trimebutine-induced stimulation of propulsive activity may depend on a contraction of longitudinal muscle which was partly inhibited by atropine (10(-6) g/ml), though metoclopramide at low doses had little effect on propulsive activity.