Evidence exists that motilin immunoreactivity is highly expressed in Purkinje cells. In this study, immunohistochemistry and whole-cell patch-clamp recording were performed to investigate the spatial distribution and electrophysiological effects of motilin receptors in the cerebellum. We show here that motilin receptors are strongly expressed in Purkinje cells of the human and rat cerebellum. Motilin at 10 nM depolarized Purkinje cells of the rat cerebellum, and this was mimicked by the motilin receptor agonist erythromycin. The depolarization evoked by motilin persisted in the presence of tetrodotoxin, glutamate and gamma-amino-n-butyric acid receptor antagonists, indicating that motilin excited the Purkinje cells by activating the receptor expressed on the neurons recorded. We suggest that motilin may serve specific neural functions in the cerebellum.