The limited amount of available information regarding the developmental control of protein kinase C (PKC) isoform expression restricts our understanding of the role of these enzymes in normal physiology. Accordingly, this study investigated PKC isoform expression in selected tissues from fetal, neonatal, and adult rats. PKC beta immunoreactivity was prominent in brain tissue, whereas the expression oi PKC alpha, PKC delta, PKC epsilon, and PKC zeta; was found robe widespread. Although no developmental change in any PKC isoform was evident in liver, striking tissue-specific age-dependent differences in PKC isoform abundance were noted in other tissues. For example, age-dependent increases in PKC alpha, PKC beta, and PKC delta in brain contrasted with age-dependent decreases in PKC alpha and PKC delta in lung, kidney, and heart. Immunoreactivity for PKC epsilon was abundant in all fetal/neonatal tissues; PKC epsilon was detected in the adult brain, heart, and liver, but not the adult kidney and lung. Finally, PKC zeta, was more abundant in fetal/neonatal than in adult brain, lung, kidney, and heart. These results indicate that the fetal/neonatal lung, kidney, and heart are enriched in PKC zeta, PKC alpha, PKC delta, and PKC epsilon, relative to the adult tissues. These age dependent variations in the abundance of individual isoforms of PKC may critically influence tissue responsiveness to external stimuli. Moreover, the finding that PKC zeta is particularly abundant in fetal tissues as well as the liver, the only tissue included in this study which retains regenerative capacity in the adult animal, is consistent with the notion that PKC zeta, may Flay a role in cell proliferation.