BACKGROUND A significant percentage of patients with refractory germ cell tumors will not respond to standard salvage regimens. Thus there is a need for new active agents. Paclitaxel has demonstrated activity against a variety of solid tumors in both laboratory and clinical studies. METHODS Eighteen patients with refractory germ cell tumors who failed initial cisplatin-based chemotherapy and a maximum of 2 salvage regimens were enrolled into a Phase II trial of paclitaxel at a dose of 170 mg/m2 by intravenous infusion over 24 hours every 21 days without growth factor support. The median age of the patients was 32.5 years (range, 18-49 years). The testis was the primary site of tumor for 13 patients (72%) and the tumor was extragonadal in 5 patients (28%). Six patients (33%) were late recurrences. Twelve patients (67%) had > or = 2 metastatic sites. The median number of previous chemotherapy cycles was six (range, four to nine). Three patients (17%) previously had undergone autologous bone marrow transplantation. RESULTS Two patients (11%) responded to paclitaxel. Major toxicities were Grade 3-4 neutropenia (55% of patients) and Grade 3-4 neurotoxicity (2 patients). Neutropenic fever occurred in 3 patients (17%). CONCLUSIONS Paclitaxel demonstrated minimal activity in heavily pretreated patients with multiple, poor risk clinical features. These results in part may be due to the unfavorable characteristics of the patients in the current study, specifically the high percentage of patients with late recurrences and extragonadal primary tumors, both of which are known to respond poorly to salvage therapy. Other trials with different patient populations and doses of paclitaxel reported response rates ranging from 13.3%-26%. The role of paclitaxel in the treatment of patients with refractory germ cell tumors remains to be defined in future studies.