Though the majority of patients with metastatic nonseminomatous germ cell tumors can be cured by modern combination chemotherapy, for those patients who do not respond to standard therapy additional drugs are needed. The activity of three new anthracycline derivatives, 4-epidoxorubicin, THP-doxorubicin and mitoxantrone against two established human testicular cancer cell lines in comparison to doxorubicin and to cisplatin, vinblastine, bleomycin and ifosfamide was studied in a xenograft model. All drugs were given at equitoxic doses. There were no differences in antitumor activity between the four anthracycline derivatives. In line H 12.1, which is very sensitive to the standard drugs cisplatin, vinblastine, bleomycin and ifosfamide, all four anthracycline derivatives were inferior to these agents. In contrast, in line H 23.1, where all four standard agents showed a significant lower antitumor activity when compared to line H 12.1, the anthracyclines preserved their activity, indicating a lack of cross resistance. Thus the anthracycline derivatives seem to be inferior to the standard drugs as first line treatment but because of apparent lack of cross resistance they deserve further evaluation in refractory germ cell tumors.