Thyrotropin-releasing hormone (TRH) is known to elicit wet-dog shakes in rats through a central mechanism of action. In the present study, the ability of muscarinic cholinergic antagonists to inhibit TRH-mediated wet-dog shakes was examined. The longer-acting TRH analog, MK-771, at doses of 1.0, 1.5 and 3.0 mg/kg elicited wet-dog shakes in a dose-dependent manner. The centrally-acting muscarinic cholinergic antagonists, atropine and scopolamine, at doses of 5 and 0.8 mg/kg, respectively, significantly reduced the ability of only the highest dose of MK-771 to elicit wet-dog shakes. When the peripherally-acting antagonists, methylscopolamine and methylatropine, were examined, they were not found to significantly reduce wet-dog shakes produced by MK-771 at doses of 5 and 0.8 mg/kg, respectively. The results of this study suggest that cholinergic antagonists inhibit MK-771-induced wet-dog shakes in a noncompetitive manner and support the view that TRH-mediated wet-dog shakes are modulated by central muscarinic cholinergic systems.