During brain development, cells that fail to reach their final destination or to establish proper connections are eliminated. It has been shown that the proinflammatory cytokine second messenger ceramides and the neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) play pivotal roles in the histogenesis of the cerebellum. However, little is known regarding the effects of these two factors on cerebellar granule cell migration. We have found that PACAP prevents the effects of C2-ceramide on granule cell motility and neurite outgrowth. These actions are attributable to opposite effects on actin distribution, tubulin polymerization, and Tau phosphorylation. These data suggest that PACAP and factors inducing ceramide production may control granule cell migration during cerebellar development.