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The present investigation was designed to provide the first empirical examination of the effects of clonidine, a selective alpha2-adrenergic agonist, on sexual arousal in women with and without prior sympathetic nervous system (SNS) stimulation by exercise. The purpose was to help elucidate the influence of adrenergic mechanisms on sexual function in women.Thirty sexually functional women participated in two experimental sessions in which subjective (self-report) and physiological (vaginal photoplethysmograph) sexual responses to erotic stimuli were measured after either clonidine (0.2 mg) or placebo administration in a randomized, double-blind, crossover protocol. Before viewing the experimental films, 15 subjects engaged in 20 minutes of intense exercise designed to elicit significant SNS activation.Clonidine significantly decreased vaginal pulse amplitude, vaginal blood volume, and subjective sexual responses to the erotic films in subjects who were in a state of heightened (via exercise), but not baseline (no exercise) SNS arousal.Clonidine can significantly inhibit subjective and physiological sexual arousal in women. These findings have implications for deriving an etiological theory of sexual function in women and for understanding the effects of psychotherapeutic drugs on female sexual function.