Tyrosine hydroxylase (TH), TH messenger RNA (TH mRNA) and dopamine (DA) were measured simultaneously in adrenal glands of individual Fischer 344 rats aged 2, 6, 13 and 23 months. Between 2 and 23 months TH activity rose 2-fold as compared to the youngest group. TH mRNA content of the adrenal gland rose 3-fold between 2 and 23 months. A 3-fold increase in adrenal DA content, the first catecholamine product of TH, provides evidence that the increases in TH gene expression are functionally significant. To determine if mechanisms that regulate gene expression are altered by aging, the effects of reserpine on induction of TH mRNA and TH activity were compared in another group of rats aged 2, 12 and 27 months. Consistent with the results of the first experiment, there were age-related increases in both TH activity and TH mRNA in the age-matched control groups. TH activity rose 2-fold and TH mRNA rose more than 6-fold between 2 and 27 months. The discrepancy in the relative magnitudes of increases in TH mRNA and TH protein suggest an uncoupling of regulation of TH mRNA and TH protein levels. Moreover, there were significant age-related differences with respect to modulation of TH gene expression by reserpine treatment. TH activity was induced by reserpine in the youngest group, but not in the two older age-groups. In contrast, reserpine caused significant induction of TH mRNA in all age groups. These results provide evidence that aging is accompanied by alterations in transcriptional and post-transcriptional mechanisms involved in regulation of TH gene expression.