Male Fischer 344 rats, were administered NIH-31, AIN-76A, or AIN-76A plus 0.25% yeast RNA diets for 3 weeks, partially hepatectomized (PH), and groups of 6 rats from each diet group were sacrificed at 0, 2, 7 and 14 days following PH. Liver weight, total DNA, total lipids, levels of thiobarbaturic acid reactive substnces (TBARS), and levels of intracellular deoxyribonucleotides were determined. In addition, the number of hepatocytes in mitosis and/or positive for nuclear proliferating cell nuclear antigen (PCNA) were determined. Liver regeneration, measured as liver weight or total liver DNA, was equal in the three diet groups and was essentially complete by the end of 14 days. However, there was a 53% reduction in the mitotic index and a two-fold increase in the ratio of proliferating cells (G1+S+G2 cells) to mitoses at 48 hours in animals of the AIN-76A diet group compared to those fed NIH-31 diet, suggesting that the cells were arrested or delayed in S-phase. At the time of PH, liver deoxyuridine monophosphate (dUMP) and deoxythymidine triphosphate (dTTP) levels in the AIN-76A group were decreased 29% and 57%, respectively, compared to those of the NIH-31 group. Addition of yeast RNA to the AIN-76A diet partially prevented the decrease in mitosis and maintained deoxyribonucleotide triphosphates (dNTP) levels to those of the NIH-31 group. These results indicate that the lack of dietary nucleotides in semipurified diets can alter dNTP levels and have adverse effects on cell proliferation. Consideration should be given to supplementing purified diets with a dietary source of nucleotides.