Thirty-two women with untreated metastatic breast cancer were treated with 100 mg/M2 i.v. methotrexate (MTX), 600 mg/M2 5-fluorouracil (5FU) and leucovorin 15 mg orally every 6 hr, 24 hr after MTX (MFL) on days 1 and 8 every 28 days. Stratification was according to sites of metastases (mets), adjuvant (adj), chemotherapy (CTX), and/or hormonal therapy or no adj therapy (Tx). Treatment continued until documented radiographic or clinical disease was in progression. Toxicity was mild, consisting of only minimal elevations of transaminases and mild cytopenias. There was no pulmonary toxicity. There were no hospitalizations, treatment delays or cessations for toxicity. One patient with skeletal mets had a complete response and 7 had partial responses. The overall median progression free survival (PFS) was 13.8 months (mos). Eighteen patients with skeletal mets had PFS from 7-70 mos (median 15.9). Five patients with lung mets only had PFS from 6-20 mos (median 9.8 mos). Patients with liver alone or with other visceral mets showed progression within 2-5 mos. However, patients with bone and visceral mets without liver involvement had PFS from 8-50 mos (median 20.5). Of 21 adj Tx failures the median PFS was 8.8 mos (2-94). Six who received adj CTX had a median PFS of 7.6 mos (3-12) and 4 tamoxifen (tam) failures a median PFS of 11 mos (8-15). Eleven patients who received adj CTX+tam had a median PFS of 8.5 mos (2-94). Six patients received tam at adj failure and MFL at progression. These six had a median PFS of 19.8 mos (8-50). The patients (six, who received no prior adj Tx) had a median PFS of 24.3 (8-70). MFL is as effective in achieving clinical remissions in metastatic breast cancer, is inexpensive and is far less toxic than other CTX regimes. MFL should strongly be considered as first line Tx.