Objective: To determine the effects of clonidine, which reduces central sympathetic activation, on the sweating threshold in postmenopausal women with and without hot flashes.Design: Laboratory physiologic study.Setting: University medical center.Patient(s): 12 healthy postmenopausal women reporting frequent hot flashes and 7 reporting none.Intervention(s): In two separate sessions, participants received a blind intravenous injection of clonidine HCl (2 μg/kg of body weight) or placebo, followed by body heating.Main Outcome Measure(s): Core body temperature, mean skin temperature, sweat rate, sternal skin conductance level, and blood pressure.Result(s): Symptomatic women had significantly lower core body temperature sweating thresholds than asymptomatic women after receiving placebo. Clonidine significantly increased this threshold in symptomatic women but lowered it in asymptomatic women.Conclusion(s): These results support the hypothesis that elevated brain norepinephrine levels reduce the sweating threshold in symptomatic women, thereby contributing to the initiation of menopausal hot flashes.