Twenty-five women with advanced histologically documented stage IV recurrent or inoperable breast cancer were enrolled on a phase II study of echinomycin administered at a dose of 1.2 mg/m2 intravenously over 30 minutes weekly for 4 weeks followed by a two week rest period. Seventy-six percent of patients had visceral dominant disease at study entry and all patients had previously received chemotherapy. One of 21 eligible patients had a partial response lasting 147 days. The median survival for this group of patients was 5.9 months and the median time to treatment failure was 1.7 months. Nausea and vomiting was the primary toxic effect and was severe or life-threatening in 43% of patients. Transient elevation of liver enzymes occurred in 30% of patients. Bone marrow suppression was not significant. Echinomycin as employed in this study did not demonstrate significant antitumor activity in previously treated patients with advanced breast cancer.