The level of leptin [the obese (ob) gene product] mRNA is markedly elevated in hypothyroid male rats. The administration of tri-iodothyronine (T-3) to hypothyroid rats resulted in a 40 % decrease in leptin mRNA at 8 h. This decrease in leptin mRNA was associated with a parallel decline in circulating leptin levels of about 50 % at 24 h. Conversely, beta(3)-adrenergic receptor mRNA levels were markedly decreased in epididymal adipose tissue from hypothyroid rats. T-3 administration resulted in a 147 % increase at 12 h in beta(3)-adrenergic receptor mRNA. There was corresponding increase due to T-3 in the lipolytic response to the specific beta(3)-adrenergic agonist CL 316,243 that paralleled the increase in beta(3)-adrenergic receptor mRNA. T-3-mediated changes in leptin and beta(3)-adrenergic receptor mRNAs were blocked by cycloheximide, suggesting the involvement of short-lived proteins in these effects. The present results indicate that T-3 has opposite effects to those of insulin on the white adipose tissue of rats with respect to leptin mRNA expression.