In amphibians, there is a close interaction between the interrenal and the thyroidal axes. Hypothalamic corticotropin-releasing hormone or related peptides stimulate thyroidal activity by increasing thyrotropin synthesis and release, while corticosterone accelerates both spontaneous and thyroid hormone-induced metamorphosis. One of the mechanisms that is thought to contribute to this acceleration is a corticosterone-induced change in peripheral deiodinating activity. The present experiments were designed to investigate further the effects of glucocorticoid treatment on amphibian deiodinase activities and to explore the possible role of these effects in metamorphosis. Neotenic axolotls (Ambystoma mexicanum) were treated either acutely or chronically with dexamethasone (DEX) and changes in type II and type III iodothyronine deiodinase (D2 and D3) activities were studied in liver, kidney, and brain. In addition, gill length, tail height, and body weight were measured at regular intervals in the chronically treated animals in search of metamorphosis-related changes. A single injection of 50 microg DEX decreased hepatic D3 activity (6-48 h) while it increased D2 activity in brain (6-48 h) and to a lesser extent in kidney (24 h). These changes were accompanied by an increase in plasma T(3) levels (48 h). Samples taken during chronic treatment with 20 or 100 microg DEX showed that both hepatic D2 and D3 activities were decreased on day 26, while renal D3 activity was decreased but only in the 20 microg dose group. All other deiodinase activities were not different from those in control animals. At 25 days, all DEX-treated axolotls showed a clear reduction in gill length, tail height, and body weight, changes typical of metamorphosis. Prolongation of the treatment up to 48 days resulted in complete gill resorption by days 44-60. Although probably several mechanisms contribute to these DEX-induced metamorphic changes, the interaction with thyroid function via a sustained downregulation of hepatic D3 may be one of them.