The effect of hyperthyroidism and hypothyroidism on conversion of T⁴ to T₃ and the degradation of rT₃ was studied in rat liver and kidney homogenates. Administration of T₄ (5 μg/100 g BW/day for 5 days) to normal rats resulted in significant increases in the rates of both reactions in liver homogenates; the increase was no greater after T₄ doses of 10 and 20 μg/100 g/day. Responses also were no greater after 12 than after 5 days of T₄ treatment. After thyroidectomy, T₃ production declined gradually to 30% of control in 6 weeks; rT₃ degradation initially decreased more rapidly, but at 4 and 6 weeks, the percentage of fall was similar for both reactions. No significant changes in either reaction were found in kidney homogenates from T₄-treated rats. In kidney homogenates from thyroidectomized rats, both reactions were significantly impaired at 6 weeks. These results extend previous observations that 5′-deiodination of T₄ and rT₃ change in parallel directions after various experimental manipulations, and further support the hypothesis that a single 5′-deiodinase catalyzes T₄ to T₃ conversion and rT₃ degradation in the liver and perhaps the kidney as well.