Twenty-seven patients with histologically proved advanced breast cancer were given VP 16-213 and cyclophosphamide. Twenty-one had shown resistance to other chemotherapy schedules and six had experienced relapse during adjuvant chemotherapy. There were four complete responses (15%) and seven partial responses (26%). Median survival was 61 weeks and median duration of response was 31.4 weeks. All patients experienced gastrointestinal toxicity and 22 patients (81%) showed bone marrow toxicity. This regimen is effective in advanced breast cancer resistant to other chemotherapy regimens.