Sixty-two women with advanced breast cancer were admitted to a pilot study in which a modified CMF regimen was administered. Cyclophosphamide was administered i.v. at a dosage of 600 mg/m2 on the same day as fluorouracil (600 mg/m2/i.v.) and methotrexate (40 mg/m2/i.v.). The therapy was recycled on the 21st day and in the presence of myelosuppression, the administration of the drugs was delayed for 1-2 weeks recovery of the hematologic values. CR + PR were obtained in 42% of patients and no change in 32% (U.I.C.C. criteria). Metastases to soft tissues showed CR + PR in 55% of the cases, bone in 33% and viscera in 35%. The menopausal status, the disease-free interval and the number of involved sites did not influence statistically the percentage of responses; however, the response rate was influenced statistically by previous treatment. The median duration of response was 7.5 months; the median overall survival of the 60 evaluable patients was 18 months. Due to myelosuppression, CMF i.v. administration was delayed 90/620 times (14%). Toxicity was acceptable and had a lower incidence than that reported in the literature in different series of CMF administered p.o. Nausea and vomiting, in particular, were limited to 24-48 h after administration of the drugs, and alopecia was seldom observed.