Although meperidine is an effective treatment of postanesthetic shivering, its mechanism of action remains unknown. Investigation of other drugs might help clarify the mechanisms by which shivering can be controlled. Accordingly, we investigated the efficacy of clonidine, an alpha 2-adrenergic agonist, and ketanserin, a 5-hydroxytryptamine antagonist, in treating postanesthetic shivering. First, 54 patients shivering after general anesthesia were allocated randomly to receive an intravenous bolus of saline, 150 micrograms clonidine, or 10 mg ketanserin. A second study explored the dose-dependence of clonidine. Forty shivering patients were given saline or clonidine, 37.5, 75, or 150 micrograms. The duration of shivering was significantly shorter in those given clonidine (2.1 +/- 0.9 min) than in the other two groups and shorter in the ketanserin group (4.3 +/- 0.9 min) than in the saline group (12.0 +/- 1.6 min). Clonidine and ketanserin significantly decreased systolic arterial blood pressure when compared to saline. Core rewarming was significantly slower in the clonidine group. In the second study, 37.5 micrograms clonidine was no more effective than saline. Two minutes after treatment, 150 micrograms obliterated shivering in all patients. Five minutes after treatment, all patients given 75 micrograms had stopped shivering. Systolic arterial pressure and heart rate decreased significantly in patients given 75 and 150 micrograms clonidine. Clonidine (150 micrograms) and ketanserin (10 mg) both are effective treatment for postanesthetic shivering. The effect of clonidine on shivering is dose-dependent: whereas 37.5 micrograms had no effect, 75 micrograms clonidine stopped shivering within 5 min.