AIM: To study the antitumor activity of sobuzoxane (Sob) in combination with doxorubicin (Dox) and the effect of Sob on Dox-induced cardiotoxicity. METHODS: DBA/2 mice bearing transplanted leukemia P388 were given iv Dox 2 mg . kg(-1). d(-1) for 3 d, 4 mg . kg(-1). d(-1) for 1 d combined with ig Sob 20, 40 mg . kg(-1). d(-1) for 7 d. The increase in life span (ILS) of each group was recorded in 30 d. The myocardium of moribund mice was examined by transmission electron microscopy. RESULTS: The ILS of combination therapeutic groups of Sob with Dox was 48.7%, 57.3%, 59.0%, and 62.4% respectively, which were 30%-90% higher than the sum of ILS of two groups treated with Dox and Sob separately (P < 0.01). The ultrastructural injury of cardiomyocytes of P388-bearing mice caused by combination chemotherapy with Dox plus Sob was markedly attenuated compared with Dox alone: CONCLUSION: Sob with Dox exhibited an antitumor synergistic effect on leukemia P388, and the cardiotoxicity of Dox was reduced by Sob.