In October 1978, the Swedish Cooperative Ovarian Cancer Study Group started a randomized comparison of doxorubicin 40 mg/m2 and melphalan 0.4 mg/kg with melphalan 1 mg/kg every four weeks in International Federation of Gynecology and Obstetrics (FIGO) stages III and IV ovarian cancer of serous and anaplastic histology. One hundred sixty-eight patients entered the study, and 148 were evaluable at five years or longer. All had residual tumors larger than 10 cm, with appropriate stratification according to stage, histologic grade, and age. Definition of response was according to World Health Organization (WHO) criteria except that we required three months' regression of all clinically detectable tumors instead of one month. Seventy-three women treated with doxorubicin plus melphalan had a significantly higher response rate than 75 patients treated with melphalan alone (54.7 versus 26.7%; P less than .0001), median duration of response (13.0 versus 7.3 months; P less than .0057), and median survival time (18.5 versus 10.5 months; P less than .0001). Combined treatment produced significantly more complete remissions than single-agent therapy (30 versus 6.7%; P less than .001). At 60 months, ten patients were alive in the doxorubicin plus melphalan group, compared with three in the melphalan group. Temporary bone marrow depression was significantly more frequent in the melphalan-treated patients, but subjective side effects were the same in both groups.