Almost two-thirds of breast cancer survivors report experiencing hot flashes, and many rate this symptom as severe or extremely bothersome. A randomized, controlled trial of two dosage regimens of venlafaxine (Effexor), a serotonin-norepinephrine reuptake inhibitor used to treat hot flashes in breast cancer survivors, was conducted with 70 women who had completed treatment for breast cancer and reported daily hot flashes. Most of the women were in their early or mid-50s, white (non-Hispanic), married, and working full-time. One group received a low dosage and the other a higher dosage. On one day each week, the women recorded in a symptom diary the frequency and severity of, as well as the degree of bother associated with, hot flashes, and on another day they wore a sternal skin conductance monitor to record body temperature elevations, a physiologic measure of hot flashes. Compared with a placebo, both dosages reduced the frequency of hot flashes as measured by self-report and by physiologic assessment, as well as hot flash severity and bother. In addition, a subgroup of women whose hot flashes decreased by at least half also reported less fatigue and sleep disturbance and improved vitality and mental state. Common adverse effects included constipation, headache, and dry mouth, and some women discontinued long-term use as a result of the adverse effects. These findings indicate that venlafaxine helps to reduce hot flashes in breast cancer survivors, although the adverse effects can be bothersome.