The neurotransmitters dopamine and serotonin control the peristaltic movement of the gut that consists of propagating waves of rhythmic contraction and relaxation. While intestinal cells of Cajal (ICC) serve as a pacemaker in the gut, the effect of dopamine on the pacemaker activity of ICC remains unknown. Here, we report that together with serotonin receptors, the dopamine receptor D_2 contributes to maintaining [Ca^(2+)]_i oscillations in ileum ICC. When the antagonist for the D_2 receptor was applied to the cell cluster or the tissue culture prepared from muscle layers of the mouse small intestine, the amplitude of [Ca^(2+)]_i oscillations in ICC declined after a transient increase. On the other hand, treatment with the D_2 receptor agonist decreased the frequency of [Ca^(2+)]_i oscillations in ICC. These results suggest that basal level activity of the D_2 receptor is crucial for maintaining [Ca^(2+)]_i oscillations in ICC. The decrease in the [Ca^(2+)]_i oscillation amplitude upon the D_2 receptor antagonist treatment was abrogated by antagonizing the serotonin receptor 5HT_2, indicating an inhibitory effect of the 5HT_2 receptor on the [Ca^(2+)]_i oscillations. Together with the finding that treatment with the antagonist for the serotonin receptor 5HT_3 completely eliminated [Ca^(2+)]_i oscillations in ICC, our results show that dopamine and serotonin receptors cooperatively regulate pacemaker activity of ICC.