In an ongoing effort to establish the most appropriate dose and administration schedule for paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ), the feasibility and safety of weekly 1-hour infusions were evaluated in 16 women with metastatic breast cancer previously treated with at least one chemotherapy regimen. Paclitaxel was administered on an outpatient basis at a starting dose of 100 mg/m2/wk for 4 consecutive weeks, with 4-week cycles continued until disease progression or the onset of intolerable toxicity. With 215 weekly infusions administered so far (median, 13 per patient), no episodes of febrile neutropenia have occurred, and no hematopoietic growth factors have been used. Plans for dose escalation were abandoned after grade 3 sensorimotor neuropathy developed in five of nine patients treated at paclitaxel 110 to 120 mg/m2. With dose escalation eliminated, further severe neurotoxicities were rare, but some degree of cumulative peripheral neuropathy was noted in all but three patients. No acute hypersensitivity reactions were noted. To date, six of 15 evaluable patients have achieved a major response to therapy, with one complete response and five partial responses. Four other patients had a minor response to therapy, one patient had an early death due to autopsy-proven extensive pulmonary microvascular carcinomatosis, and five patients have stable disease. Although the potential neurotoxicity of this regimen merits attention, the overall profile of a high therapeutic index, manageable toxicity, and convenient administration schedule makes this an attractive treatment alternative for patients with metastatic breast cancer.