This study examines (a) the effects of aging on plasma thyroid hormone concentration and (b) in vivo binding and cytoplasmic distribution of thyroid hormones as well as the conversion of thyroxine (T4) to triiodothyronine (T3) in liver and cerebral hemispheric tissue. The results show that (a) in male Long-Evans rats aging decreases plasma T4 concentration but does not affect plasma T3 concentration and (b) the in vivo nuclear T3 binding does not change significantly. However, nuclear T3 binding derived from T4 is decreased as a consequence of reduced T4 to T3 conversion in both tissues. The nuclear T4 binding is also depressed, perhaps due to the decrease in the T4 of the protein free cytoplasmic compartment. Aging was also found to change protein free and protein bound cytoplasmic distribution of T4. That is, an increase was observed in protein bound cytoplasmic T4 and a decrease in the protein free cytoplasmic T4 of both tissues. These results indicate an overall alteration in thyroid hormone production and peripheral tissue binding and processing of thyroid hormones with a consequent suboptimal thyroid state with aging.