A total of 14 women with severe premenstrual syndrome unresponsive to conservative medical therapy were treated with danazol in doses sufficient to suppress cyclic ovarian steroidogenesis. In each case medical ovarian suppression resulted in complete relief from symptoms. For ongoing symptom relief, each woman elected to undergo bilateral ovariectomy and concomitant hysterectomy. Both medical ovarian suppression and ovariectomy with low-dose conjugated estrogen therapy afforded lasting relief from cyclic symptoms of premenstrual syndrome and a corresponding improvement in overall quality of life. We conclude that cyclic ovarian steroidogenesis is a powerful determinant for the expression of premenstrual symptomatology. Ovariectomy with low-dose estrogen replacement is an effective alternative for the woman with debilitating premenstrual syndrome who does not respond to conventional interventions.