The average number of rRNA genes per haploid genome (rRNA gene dosage) of the cells present in liver and brain was determined throughout the lifespan of the inbred C57BL/6J mouse strain and of human. Ribosomal RNA gene dosage was determined using the RNA-excess DNA - RNA hybridization technique. DNA was extracted and purified using a CsCl/chloroform method with a high percent yield (over 90%) to minimize any possible effects of tissue and age-dependent selective loss or gain of rRNA genes. Radioactive rRNA was from the liver of the youngest age group for either mouse or human in all hybridization experiments, with DNA from the different tissues and age groups being the only variable. In the young mouse (35-49 days), the rRNA gene dosage was 36% higher in brain (114 genes), as compared to liver (84 genes). The rRNA gene dosage remained essentially constant as a function of age for mouse brain; but between the age of about 220 to 440 days, it increased in liver, attaining approximately an equal value to that of brain. No significant difference was found in the rRNA gene dosage of brain or liver between different mice of the same age. In contrast to this result, a significant difference was found between human tissues of similar age. The rRNA gene dosage ranged about 2-fold (148-289) between 2 months to 75 years of age. An age-dependent trend, similar to that for mouse liver, was found when the averages of four different age groups totaling 20 individuals were compared. However, this was not statistically significant. No difference in the rRNA gene dosage as a function of sex or tissue was apparent. Several models are discussed to account for these results.