We examined the immunohistochemical localization of p39, the regulatory subunit of cyclin-dependent kinase 5 (Cdk5), in the adult rat brain. Cdk5 requires either p39 or p35 to assume its active form in the mammalian CNS. We developed a specific antibody against p39, and localized p39-immunoreactivity in the rat brain. p39-immunoreactivity was observed in the neuronal somata of the cerebral cortex, hippocampus and basal ganglia, and also in the Purkinje cells. Immunopositive astrocytes and oligodendrocytes were scattered throughout the rat brain. p35 immunoactivity has been observed exclusively in neurons and was never detected in glial cells. The present results suggest that p39 and p35 may have different functional roles in the regulation of Cdk5 in the rat CNS.