FEC (5-FU 500 mg/m2, epirubicin 50 mg/m2, and cyclophosphamide 500 mg/m2) administered as a conventional bolus schedule is widely used in treatment of advanced breast cancer. 5-FU is thought to be more efficient when administered at high doses as a continuous infusion. The aim of this study was to compare the response rate, time to treatment failure, and overall survival obtained with standard FEC regimen (group A) and FEC with high-dose infusional 5-FU (750 mg/m2 per day/days 1 to 5) (group B). One hundred and seventy-eight patients entered this study, 89 in each arm; 10 were noneligible. Both groups were comparable for age, performance status, menopausal status, hormonal receptor status and prior treatment of the initial tumor, duration of relapse free interval, and type and number of disease sites. One hundred and forth patients were evaluable for efficacy. The response rate was 33.3% in group A (1.4% complete response-CR), and 39.4% in group B (9.8% CR) (ns). In an intent to treat basis (n = 168) the response rates were 26.8% and 34.1%, respectively, in groups A and B (ns). The response rate in liver metastasis was significantly higher in group B (57.1%) than in group A (20.0%) (P = 0.03). The time to treatment failure and overall survival were not different between the two groups. One hundred and fifty-three patients were evaluable for toxicity. 10.7% of the patients in group A and 16.0% in group B stopped treatment due to toxicity. Stomatitis was more frequently observed in group B than in group A (46.7% versus 2.6%, respectively, p < 10(-9)). The rates of other side effects were similar in the two groups. In conclusion, the two regimens gave similar overall response rates, time to treatment failure and survival, but infusional 5-FU yielded a better response rate in the liver metastasis.