This is a preliminary study of a new orally administered alpha-adrenergic agonist, lofexidine, to establish its effectiveness in the control of vasomotor flushes (VMF) in five post-menopausal women. The initial dose of lofexidine, 0.1 mg b.i.d., was increased by 0.1 mg b.i.d. every two weeks until VMF disappeared, until side-effects became intolerable, or until a maximum dose of 0.6 mg b.i.d. was reached. When the maximum dose for these criteria was reached, there was a patient-blinded crossover to placebo. Each patient recorded her VMF each day and was monitored by finger thermistor for three hours every two weeks to record VMF. At the maximum tolerated dose, the patients had an average 74% (P less than 0.001) decrease in subjectively noted VMF, and a 61% (P less than 0.05) decrease in VMF objectively measured by finger thermistor. The side-effects (dry mouth, fatigue, headache) became intolerable for one patient at 0.3 mg b.i.d. and for one patient at 0.5 mg b.i.d. Two patients tolerated 0.6 mg b.i.d. Four patients had a return to near baseline numbers of VMF with placebo. Preliminary evidence indicates that lofexidine is probably effective in the treatment of VMF; however, at doses which completely eliminate VMF, the side-effects may become intolerable.