Seventy five patients suffering from metastatic breast cancer previously unexposed to chemotherapy were treated with Cyclophosphamide, Methotrexate and 5-fluorouracil (CMF) upon diagnosis of their first relapse. Dose Level I (85% or more of the planned dose) was given to 14 patients (19%); Dose Level II (66% to 84% of the planned dose) to 29 patients (39%); and Dose Level III (65% or less of the planned dose) to 32 patients (42%). Before initiation of treatment, 41 patients (55%) had a good performance status (PS greater than or equal to 80%) and 34 patients (45%) had a poor performance status (PS less than 80%) according to the Karnofsky scale. The overall response rate was 44%, including 17% complete responses. There was no significant correlation between response rates and the dose levels of chemotherapy. However, patients with a good performance status had a higher response rate (61%) compared with patients with a poor performance status (25%; p = 0.0025). The actuarial 3 year survival according to dose levels of CMF was 15%, 41% and 36% for Dose Levels I, II, and III, respectively (p = 0.34), but was 52% for patients with PS greater than or equal to 80% versus 14% for patients with PS less than 80% (p = 0.0001). These data indicate that the general condition of the patient at the time of initiation of CMF chemotherapy, as reflected by the performance status, may be of greater significance for the prediction of the ultimate treatment outcome rather than the total amount of chemotherapy delivered per se.