Twenty-six patients (25 evaluable for response) with previously treated metastatic breast cancer were treated with intermediate-dose methotrexate (300 mg/m2) followed by 5-fluorouracil (600 mg/m2) and folinic acid-SF (Leucovorin) rescue (10 mg/m2 q 6 h X 6 doses) with or without tamoxifen (20 mg) and conjugated estrogen (Premarin) (.625 mg twice daily) depending on receptor status. There were two partial responses (8%) with no difference in response between patients who did or did not receive hormones. Toxicity was primarily hematological and elevation of liver function tests. The above schedule has minimal activity in previously treated metastatic breast-cancer patients.