Effects of cisapride were studied on the whole segments and muscle strips isolated from the guinea pig ascending colon. In whole segment preparations, external application of cisapride (0.4-10 microM) produced relaxation and inhibited spontaneous and evoked intraluminal pressure changes. Intraluminal application (1-10 microM) increased the pressure response. In many circular muscle strips (18 preparations out of 20), cisapride (0.3-1 microM) increased the mechanical activity, particularly when the pH was lowered, associated with an increased spike activity. However, this action was relatively weak, and in some preparations (2 preparations out of 20), almost no effect was observed. At higher concentrations (more than 1-5 microM), cisapride reduced the muscle tone and nerve-mediated contractions. The cisapride effect could be demonstrated in the presence of atropine (0.5 microM) and serotonin (5 microM). It was concluded that cisapride has direct inhibitory as well as excitatory actions. There was a tendency for the excitatory action to appear at a lower concentration than for the inhibitory action.