Typically, the role of corticosterone(B) in metamorphosis is considered secondary to that of thyroid hormone, with B having only enhancing effects. In the current study, we demonstrate that the relationship between the thyroid hormones and B is much more complex and that thyroxine (T4) may depend on B for some of its functions. Tadpoles of the western toad (Bufo boreas) were treated with various combinations of corticosterone (B), thyroxine (T4), triiodothyronine (T3), a goitrogen (thiourea; Thio), and a corticoid synthesis inhibitor (metyrapone; MTP). Hormones were extracted from individual tadpoles and whole-body hormone levels determined by radioimmunoassay. B-treatment decreased the ratio of T4 to T3, suggesting that B increased the conversion of endogenous T4 to T3. In addition, B-treatment in combination with T4 resulted in high whole body-levels of T3. B also caused a decrease in whole body-thyroid hormone levels (T4 and T3), suggesting negative feedback on the hypothalamo-pituitary-thyroid axis and T3 had a similar effect, decreasing whole body-T4 levels. T4-treatment, but not T3, increased whole body-B levels and MTP-treatment in combination with T4 prevented the stimulatory effect of T4 on B production. MTP-treatment alone blocked all steroid metabolism of [3H]progesterone by the inter-renal in vitro, and lowered whole body-B levels three-fold in vivo. Thio-treatment reduced thyroid hormone levels and also resulted in decreased B. Finally, we suggest that these results demonstrate a system in which T4 may regulate its own potency: increasing T4 stimulates B production, which increases the conversion of T4 to its more active form T3.(ABSTRACT TRUNCATED AT 250 WORDS)