Some women experience premenstrual mood symptoms that severely disrupt their lives and relationships. These women often require pharmacologic treatment. Selective serotonin reuptake inhibitors, particularly daily fluoxetine, have been proven superior to placebo in several randomized controlled trials. Twenty-four women with confirmed premenstrual dysphoric disorder (PMDD) and with a history of affective disorders or alcoholism were treated with fluoxetine 20 mg/day (continuous), and 24 women with PMDD and no psychiatric history were treated with fluoxetine 20 mg/day for 14 days premenstrually only (intermittent). Both groups received treatment for three menstrual cycles. Sixteen women (66.7%) in the continuous dosing group and 18 women (75.0%) in the intermittent group were classified as treatment responders. Intermittent dosing of fluoxetine seems to be effective and mostly free of side effects in women with PMDD and, therefore, may offer an attractive treatment option for a disorder that is itself intermittent.