The results of a prospective controlled study with alternating cycles of two effective non-cross resistant combinations in advanced breast cancer are reported. The two combinations consisted of adriamycin plus vincristine (AV) and cyclophosphamide, methotrexate and fluorouracil (CMF). The study was carried out with the main intent to obtain a higher incidence and a longer duration of response compared to that obtained with either combination alone. A total of 110 evaluable patients (55 for each treatment group) not previously treated with chemotherapy were randomly allocated to receive either Therapy A (2 AV followed by 2 CMF) or Therapy B (2 CMF followed by 2 AV). Complete plus partial response (53% vs 60%) as well as duration of remission (11 vs 12 months) were similar in both treatment groups. At the time of present analysis, 20 patients died from cancer (Therapy A: 9; Therapy B: 11) and in 9 of them death occurred during the first 12 months. The administration of sequential combinations was no more toxic than the administration of either combination alone.