One hundred fifty-seven premenopausal women with metastatic breast cancer were prospectively randomized to treatment consisting of oophorectomy + vincristine, prednisone, cyclophosphamide, methotrexate, 5-fluorouracil (VPCMF) (Reg. I) or oophorectomy + cyclophosphamide (Reg. II) or oophorectomy followed by an observation period (Phase 1), followed by VPCMF (Phase 2) (Reg. III). Complete plus partial response rates were 72% on Reg. I, 65% on Reg. II, 18% on Reg. III, Phase 1 and 50% on Reg. III, Phase 2. Median duration of response for Reg. I was 17 months, for Reg. II 16 months, and for Phase 1 and Phase 2 of Reg. III, respectively, 5 months and 8 months. The response rate for patients treated with oophorectomy plus chemotherapy is significantly higher than the response rate achieved with oophorectomy alone as first treatment following the appearance of metastases in premenopausal women.