The teratocarcinoma cell line 833K and its relatively cisplatin-resistant subline 833K/63CP 10 were used to assess the cytotoxicity of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ), cisplatin, and 4-hydroxyperoxycyclophosphamide quantitatively. The results showed that paclitaxel had marked cytotoxicity against teratocarcinoma, particularly in the cells that were relatively cisplatin resistant. These studies suggested synergy in cytotoxicity for paclitaxel, cisplatin, and 4-hydroxyperoxycyclophosphamide. A phase II trial of paclitaxel was conducted in patients with previously treated germ cell tumors with restricted prior treatment. The paclitaxel dose was 250 mg/m2 given by 24-hour continuous infusion. In 31 patients treated with paclitaxel, eight (26%) achieved a major (complete or partial) response. The antitumor activity of paclitaxel in the phase II trial has led us to further study it as a part of combination therapy. Since the in vitro studies showed synergistic cytotoxicity, combination studies of paclitaxel, ifosfamide, and platinum are under way as salvage treatment for patients with germ cell tumors.