Thyroid hormones play a complex role in the toxicity of polychlorinated dibenzo-p-dioxins and furans and related compounds. We investigated the toxicological significance of 5'-deiodinases I and II (5'-DI and 5'-DII) in the altered thyroid hormone status of TCDD-treated rats. Time courses and dose responses were determined for serum thyroxine (T4) and triiodothyronine (T3) levels, for 5'-DI activity in thyroid gland, liver and kidney, and for 5'-DII activity in brown adipose tissue (BAT). TCDD-treatment resulted in prompt and dose-dependent decrease in circulating T4 followed by a decrease in liver 5'-DI activity 1-2 days later and an apparent increase in BAT 5'-DII activity. Changes in liver 5'-DI and BAT 5'-DII activity were secondary to decreased T4 levels. Thyroid and kidney 5'-DI activities as well as circulating T3 levels were not affected. The results suggest that altered 5'-DI or 5'-DII activities do not significantly influence the circulating levels of T4 or T3 in TCDD-treated rats.