The response rate and survival obtained with the second-line chemotherapeutic regimen etoposide combined with ifosfamide were analyzed in a series of 32 patients progressing or relapsing after cisplatin-based front-line treatment. Etoposide (100 mg/m2) was given i.v. for 3 days and 1.0 g/m2 i.v. ifosfamide, for 5 days, with 200 mg/m2 mesna being given i.v. at 0, 4, and 8 h after ifosfamide. The median age of the patients was 53.5 years (range, 26-72 years). In all, 32 patients were evaluable for toxicity and 29, for response; all patients had measurable lesions and all had previously received cisplatin-based chemotherapy. The overall objective response rate was 21%; the median duration of response was 6+ months (range, 2(+)-11 months), with that for stable disease being 5 months (range, 2-9+). The only patient who achieved a complete response is still alive after 13 months. The median survival for partial responders was 9+ months (range, 4(+)-13), and that for stable disease was 6+ months (range, 3(+)-14+). No major toxicity was observed, but myelosuppression caused dose reduction in 50% of the patients. Although the median follow-up time was short, this combination produced relatively low toxicity, with a 21% objective response rate in second-line chemotherapy after cisplatin failure, which means that this regimen is not cross-resistant to cisplatin.