We have previously demonstrated that T3 sulfate (T3S) exhibits thyromimetic effects in hypothyroid rats and that, on a molar basis, its activity approximates 20% that of T3. Since T3S is avidly deiodinated by 5'-deiodinase, type I (5'-DI) and 5'-DI activity is markedly reduced in hypothyroidism, it seemed possible that T3S is active only in hypothyroidism and not in the euthyroid state wherein normal tissue 5'-DI activity will rapidly degrade T3S and little T3S will be left for metabolism (desulfation) to biologically active T3. This study was undertaken to test this possibility. We studied the effect of T3S (4.6, 14, or 42 nmol/day for 7 days, ip) and T3 (1.0, 3.0 or 9.0 nmol/day for 7 days, ip) in groups of male Sprague-Dawley rats (5-6/group); the control group was treated with saline ip. Treatment with both T3 and T3S caused a significant (p < 0.05) increase in hepatic and renal 5'-DI. Similarly, both treatments caused a significant reduction in serum total T4 and TSH levels. In these effects, T3S was approximately one-fifth as potent as T3 on a molar basis. Interestingly, changes in body weight during treatment with T3 and T3S suggested that at doses that caused a comparable tissue or pituitary effect, T3S treatment permitted a significantly greater weight gain than treatment with T3. We conclude that T3S exhibits thyromimetic effects in euthyroid rats in a manner comparable to that in hypothyroid rats. The biological effects of T3S may be due to T3 generated in tissues by desulfation of T3S.