AbstractCyclic AMP is one of the factors which regulate cell differentiation. In animals the apparent mechanism of action of cyclic AMP is the activation of protein kinase enzymes. Postnatal changes in cyclic AMP‐dependent protein kinase enzymes were therefore examined. Determinations were made of the protein kinase and cyclic AMP‐binding specific activities and of the isozyme content (as analyzed by DEAE‐cellulose chromatography) for cytosol fractions from different neonatal and adult mouse tissues. Slight or negligible differences in enzymatic activity and isozyme distribution were observed in comparisons between neonatal and adult samples obtained from brain, liver and lung. In contrast to these tissues, however, major ontogenetic changes were observed with heart. The protein kinase and cyclic AMP‐binding I activities were constant from birth until the end of postnatal week 2. Protein kinase activity decreased 40% between days 12 and 21, and cyclic AMP‐binding activity decreased 30% between days 17 and 25. Both activities then decreased gradually with age. By ten months the kinase activity had decreased 75%, and the cyclic AMP‐binding activity 60%, from the perinatal levels. In addition to these changes in specific activity there were also age‐dependent changes in the heart isozyme distribution. The apparent amounts of the Type I and Type II isozymes decreased 75% and 25%, respectively, with age. Thus, while neonatal heart cytosol contained two to three times more Type I activity than Type II, the relative activities of the two isozymes in adults were nearly equal. The fact that the most dramatic changes in the protein kinase and cyclic AMP‐binding specific activities occur at that time period when cardiac growth shifts from a mainly hyperplastic to a predominantly hypertrophic process suggests that this enzyme may have a regulatory role in heart development.