Three protein kinase C (PKC) isozymes, type I, II, and III, have been identified as the major Ca2+/phospholipid-stimulated protein kinases in the various animal tissues. Based on the immunochemical analysis it was demonstrated that PKC I was encoded by γ cDNA, PKC II by the alternatively spliced βI and βII cDNAs, and PKC III by α cDNA. The expression of these enzymes appears to be tissue-specific and developmentally regulated. The central nervous system expresses high level of all three isozymes and the peripheral tissues mainly PKC II and III. During brain development, the expression of PKC I appears to follow the progress of synaptogenesis, whereas PKC II and III increase progressively from fetus up to 2–3 weeks of age. The level of PKC I in adult brain is highest in the cerebellum, hippocampus, amygdala, and cerebral cortex especially in those cortical regions being important for visual information processing and storage. The role of PKC II and III in cellular regulation was investigated by treatment of rat basophilic leukemia cells with the phorbol ester, phorbol 12-myristate 13-acetate. This phorbol ester caused a faster degradation of PKC II than III, indicating a differential down-regulation of these two enzymes by this compound. The results presented in this study support the contention that each species of PKC has a distinct function in the regulation of a variety of cellular processes.