Phosphatidylinositol 3-kinase (PI3-kinase) is a heterodimeric enzyme composed of a catalytic subunit of 110 kDa and an adaptor regulatory subunit. We investigated the presence and localization of five isoforms of the regulatory subunits, p55 alpha, p55 gamma, p85 alpha, p85 beta, and p50 alpha, in the rat brain. In situ hybridization histochemistry using isoform-specific cRNA probes revealed that all five isoforms were expressed in the neurons of the brain. Interestingly, most neuronal cells including Purkinje cells in the cerebellum and pyramidal cells in the cerebrum expressed all five isoforms. Immunohistochemical staining also showed the localization of p55 alpha, p55 gamma, p85 alpha, and p50 alpha in the neuronal cells in the brain. Expression of multiple isoforms in neurons suggests that they may play important roles in signal transduction in the brain. (C) 1998 Academic Press.