Despite generally high cure rates in patients with metastatic germ cell cancer, patients with incomplete response to first-line cisplatin-based chemotherapy or with relapsed disease following high-dose salvage therapy exhibit a very poor prognosis. We investigated the efficacy and toxicity of bendamustine, a bifunctional alkylating benzimidol derivative with only partial cross-resistance to other alkylating agents such as ifosfamide or cyclophosphamide. Nineteen patients with cisplatin-refractory germ cell tumors (GCT) or relapse after high-dose chemotherapy plus autologous stem cell support were treated with bendamustine at a dose of 120 mg/m2 on 2 consecutive days at 3 week intervals. Patients had received a median of 9 (range 4-20) platinum-containing treatment cycles prior to bendamustine and 13 patients (68%) had previously received carboplatin/etoposide-based high-dose chemotherapy. One patient achieved a partial remission of only 6 weeks duration. No other responses were seen. Toxicity was low with one patient developing WHO grade 3 thrombocytopenia as the only WHO grade 3/4 toxicity observed. Hematologic toxicity was similar in patients pretreated with and without high-dose chemotherapy plus autologous stem cell support. We conclude that bendamustine has little or no clinically relevant activity in patients with cisplatin-refractory GCT or relapsed disease after high-dose chemotherapy.