Messenger RNA levels and methylation patterns of the glyceraldehyde-3-phosphate-dehydrogenase (GAPDH) and beta-actin genes were studied in spleen, liver and brain of 6-, 24- and 36-month old female inbred rats. In the spleen, the mRNA levels of both housekeeping genes significantly increased between 24 and 36 months. No age-related alterations in the expression of GAPDH or beta-actin mRNA were observed in brain or liver. A considerable intertissue and interindividual variation was observed in the mRNA levels of these genes in all age-groups as compared to the level of 28 S rRNA, which was used as an internal control. In this respect the interindividual variation in the level of GAPDH mRNA paralleled the variation observed in the beta-actin mRNA level in the three tissues studied. The methylation pattern of beta-actin was found to be tissue-specific in contrast to that of GAPDH, which was identical in all three tissues. No significant age-related alterations were observed in the GAPDH methylation pattern, whereas beta-actin appeared to become slightly demethylated with age in the spleen at the CpG site for which tissue-specificity was observed.