131I chimeric L6 (ChL6) monoclonal antibody (MoAb) therapy has been performed in 12 patients with advanced, metastatic breast cancer. The protocol was designed to determine the maximum tolerated dose (MTD) of radioimmunotherapy that could be administered at 4 intervals. Ten patients received 20-70 mCi/m2 of 131I ChL6. Two of the patients received granulocyte colony stimulating factor (GCSF) on days 10-20 post therapy. The MTD for two doses was 60 mCi/m2 and thrombocytopenia was the dose limiting toxicity in the absence of marrow reconstitution with stem cells. Two patients received 150 mCi/m2 with autologous peripheral blood stem cell support 7 and 9 days post treatment. The MTD has not been reached for 131I-ChL6 with autologous stem cell support. In the 12 patients treated with 131I ChL6, six patients (50%) had measurable tumor regressions greater than 30% of the sum of the largest two dimensional products for measurable tumors. Four of these 6 patients had a partial response (PR), i.e., > or = 50% reduction in tumor size. These therapeutic responses associated with modest clinical toxicity in heavily pretreated patients suggest that clinically relevant radioimmunotherapeutic approaches can be devised for metastatic breast cancer.