The antitumour activity of S 16020-2, a new topoisomerase II inhibitor, was evaluated in comparison with doxorubicin against 13 human tumours, including colon (HT-29, Colo320DM), breast (MCF7, MDAMB-231), ovary (SK-OV-3, A2780, NIH:OVCAR-3), non-small cell lung (NCI-H460, AS49, Calu-6, NCI-H125) and small-cell lung (NCI-H69, SCLC6) cancers. S 16020-2 was administered weekly intravenous within a dose range of 20–90 mg/kg for 3 weeks. Antitumour responses were obtained in all the tumour types tested except in the two colon cancers. S 16020-2 produced significant growth delays in nine tumour models and induced regressions of all AS49 lung tumours. The antitumour activity of S 16020-2 was superior to that of doxorubicin against the NCI-H460, AS49, NCI-H69, SCLC6 and NIH:OVCAR-3 xenografts. These results demonstrate the broad spectrum of antitumour activity of S 16020-2 in a large panel of in vivo experimental models and confirm its interest as a potential agent in the treatment of malignant disease.