In developing cerebral cortex, precise control of proliferation is required because the number of precursors determines the final number of neurons, regulating final size 1. Although mitogens have been defined, their sustained expression throughout neurogenesis 2, 3, 4 suggests that additional signals directly inhibit mitogenesis. Our findings of embryonic expression of the pituitary adenylate cyclase-activating polypeptide (PACAP) ligand/receptor system and mitotic inhibition mediated by endogenous peptide and the cAMP pathway in vivo indicate that anti-mitogenic signals actively restrain growth factor-induced proliferation during development.