Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide that functions as not only a neurotransmitter/neuromodulator but also a neurotrophic factor. To assess the roles of endogenous PACAP, several groups including ours have independently produced mice with targeted mutations in the PACAP gene. The phenotypes of the mutant mice both confirm and extend our knowledge of the physiological roles of PACAP in the central nervous system as well as many peripheral organs. In this review, we briefly summarize the roles of PACAP in higher brain function, which have been proposed by the studies using the mutant mice as well as histological and pharmacological approaches.