A phase II trial of 6 months of alternating etoposide plus cisplatin (EP) and cyclophosphamide, vinblastine, actinomycin D, bleomycin, cisplatin (VAB-6) was conducted in 41 evaluable patients in an attempt to improve the treatment results in those patients considered to have "poor-risk" germ cell tumors (GCT). Eight of 14 (57%) patients with mediastinal and retroperitoneal GCTs achieved complete remission (CR), and five (36%) remain alive and free of disease. Fourteen of 27 patients (52%) with poor-risk testicular cancer achieved CR, and ten (37%) remain alive and free of disease. Two patients with seminoma, one each with a testicular and extragonadal primary tumor, achieved durable CRs. Toxicity was tolerable, but greater than that of VAB-6 alone. The response and survival of the 39 patients with nonseminomatous tumors were found to be identical to the results of 29 patients with nonseminomatous GCTs and poor-risk characteristics who were treated with VAB-6 alone. Thus, this 6-month schedule of alternating months of chemotherapy is not recommended for patients with poor-risk GCTs. Patients with such tumors should be referred to centers conducting prospective trials, so that research seeking better therapy may continue.