CCK has widespread effects in the gastrointestinal tract, stimulating pancreatic secretion and contraction of smooth muscles. The cellular mechanisms by which CCK causes smooth muscle contraction are poorly understood. We investigated the effects of CCK on guinea pig gastric smooth muscle cells using patch-clamp techniques. CCK caused contraction of cells accompanied by inward current. The conductance activated by CCK was nonselective for cations and showed little voltage dependence. Because ACh also activates nonselective cation current, we examined interactions between CCK and ACh. When CCK activated inward current, ACh caused no further effect. When CCK failed to activate current, subsequent ACh-activated current was larger and no longer exhibited its characteristic voltage dependence. Intracellular dialysis with guanosine 5'-O-(3-thiotriphosphate) caused similar changes in the voltage dependence of the ACh-activated current, suggesting a role for G proteins in regulation of the current. Activation of nonselective cation current would depolarize muscle and may contribute to the excitation mediated by CCK in tissues. These findings provide evidence that multiple types of receptors converge to regulate nonselective cation current.