Patients (18) with advanced germ cell cancer (12 primary gonadal, 6 extragonadal) that was refractory to vinblastine (V), cisplatin (P) and bleomycin (B) were treated with Etoposide (VP-16-213) and cisplatin .+-. bleomycin sulfate .+-. doxorubicin hydrochloride. All patients experienced nausea, vomiting, alopecia and myelosuppression. There were no treatment-related deaths. Five (42%) of 12 patients with primary gonadal germ cell cancer achieved a complete remission and are alive with no evidence of disease. None of the 6 patients with extragonadal germ-cell cancer achieved a complete response. Thirteen patients died 6.2 mo. (median) after starting Etoposide treatment. Etoposide-containing chemotherapy is useful in patients with primary gonadal germ cell cancer. Alternative therapies are needed for patients with extragonadal germ cell cancer.