Complete remissions in patients with metastatic breast cancer using endocrine therapy or chemotherapy are infrequent. Breast tumors are known to be heterogeneous with respect to estrogen receptor status, and the low complete remission rate may be related to this biochemical heterogeneity. Based on laboratory experiments using human breast cancer cells in tissue culture, a phase II protocol was designed using tamoxifen, premarin, methotrexate, and 5-fluorouracil. Thus far, twenty-nine (29) patients have been entered into this study and twenty-five (25) are currently evaluable for response. Overall response rate was 72%, and 14 of 25 (56%) attained a complete remission. Toxicity was minimal. Median nadir white blood cell count was 5,800 and median nadir platelet count was 252,000. In summary, this combination chemo-hormonal therapy regimen is effective with a more than 50% complete remission rate and minimal toxicity. © 1982 Martinus Nijhoff Publishers.