The objectives of this study were to determine the influence of growth and aging on ploidy, cell number, and protein content of various organs. Tissue homogenates were prepared at 3, 8, 25, 50, and 100 weeks of age. Samples were analyzed for DNA per nucleus (by flow cytofluorometry), nuclei number, and protein content. Livers of 8and 100-week-old animals were also perfused with collagenase and the released cells separated into parenchymal and nonparenchymal populations by unit gravity sedimentation. Nuclei of these cells were also analyzed for DNA. In all four zones of the kidney and in thyroid, 4n nuclei diminished in percentage between 3 and 50 weeks and increased at 100 weeks. In the growth phase these probably are cycling cells and after 50 weeks represent an increasing population of nuclei arrested after synthesis of DNA. Constant levels of ploidy were found in brain, heart, rectus abdominis, and adrenal throughout the 3-100 weeks. A dramatic increase in 4n nuclei occurred between 3 and 8 weeks in liver with little change occurring thereafter. Ploidy is a property of only parenchymal cells in liver and this probably is also true in other organs. The 4n nuclei that remain in constant proportion to the total population are established early in life and are not related to aging. They are probably tetraploid and replicate into 4n daughter cells during growth. Cerebrum shows no changes in nuclei number but exhibits a 70% increase in protein between 3 and 100 weeks. Although kidney, liver and adrenal show large increases in number of nuclei (= fourfold) with growth, these are not as great as increases in body weight (= 11-fold). With regard to organ protein, only liver shows increases approximating those in body weight. Increases in organ nuclei appear to occur in concert for adrenal, kidney, and liver whereas increases in organ protein bear no relationship to each other. bonuclease-A (RNAase, Sigma Chemical Company; 1 mg/ml) in phosphate buffered saline (PBS, 4.29 mM NazHP04, 137 mM NaC1, 2.68 mM KCl, 15 pM MgC12, pH 7.4). The following concentrations of RNAase were