This phase II study assessed the activity and toxicity profile of the sequential administration of 3 cycles of docetaxel (100 mg/m2 every 3 weeks) followed by 3 cycles of AC (doxorubicin/cyclophosphamide; 60/600 mg/m2 every 3 weeks) as first-line chemotherapy in 30 patients with metastatic breast cancer. The response rate was 60% after docetaxel and 73% after AC. This reflected an increase in the rate of complete response (from 7% after docetaxel to 17% after AC). The median duration of response was 10.5 months, and the median time to progression was 12.6 months. The median survival time had not been reached after a median follow-up of 23.2 months. The sequential treatment was generally well tolerated, with grade 3/4 neutropenia found in 20% and 14% of patients treated with docetaxel and AC, respectively. No cumulative myelosuppression was detected. The incidence of grade 3/4 nonhematologic toxicities was low. The sequential administration of docetaxel followed by AC showed a high antitumor activity and a good safety profile. The hematologic toxicity found is markedly lower than that found using concomitant chemotherapy with the same drugs. Our results support the design of phase III trials that directly compare a sequential schedule with a concomitant schedule of docetaxel plus AC (or with doxorubicin only), focusing on the toxicity profile.