Some authors have reported increased serum thyrotrophin (TSH) in animals chronically treated with lithium, suggesting that lithium might decrease pituitary thyroxine (T(4))-5'-deiodinase activity. On the other hand, the effect of lithium treatment on thyroidal T(4)-5'-deiodinase activity is also unknown. The present study was undertaken to evaluate the effects of lithium treatment on pituitary and thyroid T(4)-5'-deiodinase activity. Serum and pituitary TSH levels and thyroidal and pituitary T(4)-5'-deiodinase activities were determined in 3-month-old isogenic male Dutch-Miranda rats treated with lithium for 8 weeks. Chronic lithium treatment produced a slight increase in pituitary TSH content, but no change in serum TSH, and a significant increase in the thyroidal T(4)-5'-deiodinase activity. However, the pituitary T(4)-5'-deiodinase activity was unaffected by lithium administration. As far as we know, the present data show for the first time that chronic lithium treatment can increase the thyroxine to tri-iodothyronine conversion in the murine thyroid gland, be it directly or indirectly.