Seventeen healthy postmenopausal women who had subjectively noted eight or more hot flashes per day and who objectively demonstrated four or more vasomotor flushes of 1.0C or more during eight hours of continuous thermography were studied. They were randomly allocated in a double-blind fashion to either 50 micrograms/day of transdermal estradiol (E2) patch or placebo. Application of the first patch was followed immediately by repeat eight-hour thermography, with hourly measurements of E2 and luteinizing hormone (LH). In the transdermal E2 group only, significant elevations of E2 (mean 91 pg/mL) were noted at two hours, and LH was suppressed after eight hours (P less than .05). There was no immediate effect on vasomotor flushes. Treatment was continued for six weeks, with daily subjective recording of hot flash frequency. Patients on transdermal E2 reported a significant (P less than .001) fall in hot flashes over four weeks, after which the rate stabilized. An initial decline in the placebo group was not statistically different from baseline. Eight-hour thermography was repeated after six weeks of treatment. Patients on transdermal E2 demonstrated an 85% decrease from baseline in vasomotor flushes (P less than .01). No effect on total cholesterol or its subfractions, renin substrate, or aldosterone was found. Serum E2 levels fell by 50% in 24 hours after patch removal. Endometrial histology and vaginal cytology showed an estrogen effect.