Localization of protein kinase C (PKC) isozymes in the human nervous system, focused upon the cerebellum, hippocampus, and spinal cord was studied with monoclonal antibodies (MC-1a, -2a, -3a) against isozymes types I, II and III of PKC, respectively. Tissues were sliced by cryostat and fixed with paraformaldehyde, incubated with these antibodies, and processed for avidin-biotin peroxidase complex staining. Type I was densely localized in the cytoplasm of Purkinje cells, with their dendrites and axon terminals around the dentate nucleus of the cerebellum. Neurons of the hippocampus, especially in CA-1 to 3, and anterior horn cells of the spinal cord were also stained positively with type 1. Type II was localized randomly in some neurons of the hippocampus (CA-2 and 3), and in the substantia gelatinosa in the posterior horn of the spinal cord. Type III was diffusely present in glial tissues of the perivascular region of the brain and in the subpial layer of the spinal cord. PKC isozyme immunohistochemistry can be applied to human autopsy materials. The distinct localizations of PKC isozymes in human nervous tissues may suggest different roles in signal transduction for regulation of different cellular responses, and it may cause either normal or pathologic processes.