Gastrointestinal (GI) motility is regulated by serotonin (5-hydroxytryptamine, 5-HT), which is primarily produced by enterochromaffin (EC) cells in the GI tract. However, the precise roles of EC cell-derived 5-HT in regulating gastric motility remain a major point of conjecture. Using a novel transgenic mouse line, we investigated the distribution of EC cells and the pathophysiological roles of 5-HT deficiency in gastric motility in mice and humans.