The expression of several proto-oncogenes involved in normal cell growth was examined as a function of age in male Fischer-344 rats aged 3, 6-9, 12 and 21-23 months. Northern blot analysis using RNA isolated from pooled livers or brains showed that the transcript levels of c-myc, but not c-sis or c-src-related genes, were markedly elevated in the liver with age. In contrast, there was no substantial change in transcript levels of any of these genes in aging brain. When c-myc expression was analyzed in livers from individual rats ranging in age from 4 to 22 months, a significant (p less than 0.01) 5-fold increase in c-myc transcript levels in relation to age was detected. The results indicate that expression of c-myc in rat liver is modulated during aging and more generally, that aging in rats is associated with organ-specific changes in the transcript levels of particular genes.