The response of ifosfamide-based chemotherapeutic regimens was retrospectively analyzed in adult patients with advanced soft-tissue sarcoma who were treated at the West German Tumor Center, Essen, between 1978 and 1990. Single-agent ifosfamide was given either in split doses of 60-80 mg/kg by 4-h infusion over 5 days or as a continuous 24-h infusion of 5 g/m2. Ifosfamide was given either in split doses of 40-50 mg/kg over 5 days or as a continuous infusion of 5 g/m2 in combination with doxorubicin (40-60 mg/m2, day 1), cisplatin (20 mg/m2, days 1-5), or etoposide (100 mg/m2, days 1, 3, and 5). Mesna was given to all patients as prophylaxis against urotoxicity. Of 54 evaluable patients receiving single-agent ifosfamide, 5 achieved a complete response (CR) and 10 showed a partial response (PR), for an overall response rate of 28%. Objective responses were more frequent in previously untreated patients (47%) than in pretreated patients (15%; P < 0.01). The addition of doxorubicin (n = 41) or cisplatin (n = 29) to ifosfamide did not significantly increase the response rate (29% and 41%, respectively) or median duration of remission as compared with ifosfamide alone. In addition, no significant difference was observed between the two ifosfamide regimens used: the 24-h continuous-infusion schedule (5 g/m2 per course, 27% response rate) and the 5-day fractionated regimen (10-15 g/m2 per course, 19% response rate). We conclude that the response and the median duration of remission produced by single-agent ifosfamide compare favorably with the results achieved using single-agent doxorubicin and the usually more toxic combination regimens.