The commonly reported second-line chemotherapy regimens administered for metastatic breast cancer usually induce few responses, which last no more than 4 to 8 months. We used carboplatin 50 mg/m2 on days 2, 3, and 4 of each course, leucovorin 500 mg/m2 on days 1 through 5 in 30-minute infusions, and 5-fluorouracil (5-FU) 375 mg/m2 intravenous bolus 1 hour after each leucovorin dose to treat 32 patients with metastatic breast cancer. Six patients had previously received treatment with only one cytotoxic chemotherapy regimen, usually CMF (cyclophosphamide/methotrexate/5-FU). Twenty-six patients had received treatment with two or more regimens of chemotherapy previously, and most of them also had received radiotherapy and endocrine manipulations. Fifteen patients had visceral deposits. In cases of excessive or persistent toxicity, single daily doses were not reduced, but the start of the next course was delayed or its duration reduced. Of 26 heavily pretreated patients, 12 responded, primarily those with disease in lymph nodes, skin, breast, and pleura. One patient with liver deposits had a complete remission confirmed at laparoscopy and echogram. Survival was probably prolonged, with a median duration of response of 5 months (range, 3 to 22+), and moderate side effects that did not compromise quality of life during treatment. The probability of response was not related to the type of pretreatment (with or without 5-FU) nor to response to previous treatments.