84 patients with large operable breast cancer have been treated with primary medical chemotherapy rather than mastectomy in three sequential studies. 86% had tumours greater than 4 cm in diameter; median diameter was 6 cm (range 1-12). Median age was 46 years (range 23-66). In the first two studies 64 patients were treated with either CMF [cyclophosphamide 100 mg orally days 1-14, methotrexate 50 mg intravenously (i.v.) days 1 and 8, and 5-fluorouracil 1 g i.v. days 1 and 8, repeating at 28-day intervals for six courses] or MMM (mitozantrone 8 mg/m2 i.v. once every 3 weeks, methotrexate 50 mg i.v. once every 3 weeks, mitomycin C 8 mg/m2 once every 6 weeks, for 8 courses). 69% achieved an overall response including 17% complete remissions. 27% have had local relapse but only 3% uncontrolled local relapse. Only 14% have required mastectomy. In the third study which is ongoing, 19 patients have been treated with infusional FEC (5-fluorouracil 200 mg/m2 i.v. 24 hourly by continuous infusion via a Hickman line for 6 months, epirubicin 50 mg/m2 i.v. bolus once every 3 weeks for 6 months, cisplatin 60 mg/m2 i.v. once every 3 weeks for 6 months with appropriate intravenous hydration). Overall response rate so far is 84% with 58% complete remissions. There have been no local relapses and no patient has required mastectomy. This study demonstrates that primary medical chemotherapy can be used to avoid mastectomy in the great majority of patients presenting with large operable primary breast cancer. Infusional FEC may be more active than conventional chemotherapy in terms of overall response and complete remission rate, and infusional FEC chemotherapy now needs to be compared with conventional chemotherapy. The concept of primary medical therapy should also be compared with conventional mastectomy followed by adjuvant chemotherapy.