A single dose of ethanol increases cellular levels of the mRNA encoding thyrotropin-releasing hormone (TRH) in neurons of the paraventricular nucleus (PVN), but blocks the cold-induced increase in the levels of this mRNA. Because the thyrotropic response to cold is dependent upon TRH secretion, we hypothesized that ethanol uncouples the stimulus-induced regulation of TRH secretion from the stimulus-induced regulation of TRH expression. We employed two complementary strategies to test this hypothesis. The first was to determine whether ethanol alters pituitary sensitivity to TRH. Animals given a single intraperitoneal injection of ethanol (3 g/kg) that produced a blood alcohol concentration of nearly 300 mg/100 mL exhibited the same increase in circulating levels of TSH following an intravenous infusion of TRH. Thus, ethanol does not appear to alter pituitary sensitivity to TRH. Second, we tested whether ethanol blocks the cold induction of c-fos expression in TRH neurons of the PVN. Both cold exposure and ethanol induced the expression of c-fos in the PVN and in TRH neurons; the effects of cold and ethanol on c-fos expression were additive. Thus, ethanol clearly does not block the cold activation of TRH neurons.