Background: The combination of doxorubicin/ifosfamide is an effective chemotherapy regimen in metastatic soft-tissue sarcomas (STS), generally resulting in remission rates between 30 and 40%. A serious disadvantage of the combination are severe side effects, notably hematotoxicity, often leading to potentially life-threatening infectious complications due to leukopenia. Patients and Methods: Between May 1992 and October 1995, 45 previously untreated patients with advanced/ metastatic STS were treated every 3 weeks with a combination of doxorubicin 30 mg/m2 on days 1 and 2 and ifosfamide 3 g/m2 on days 1-3. The first course of chemotherapy was given without G-CSF support. When IV° leukopenia or fever > 38 °C after any course of chemotherapy developed, 5 μg/kg G-CSF was administered s. c. on days 4-12 after all subsequent courses. Results: Treatment resulted in severe hematotoxicity. All patients developed at least once III/IV° leukopenia and 33% developed III/IV° thrombocytopenia. The 167 courses of chemotherapy were followed by 33 (20%) episodes of fever > 38°C. Particularly the first cycle led to 17 (38%) IV° leukopenia and febrile events. In 29/45 patients treatment could only be continued by G-CSF support. Remission rate was 32%. In 15 patients metastasectomy was performed after chemotherapy. In 8/9 thoracotomies and in 2/6 laparotomies complete removal of metastases was possible. Probability of median survival for all patients is 14 months, for those who underwent metastasectomy it is 17 months. Conclusions: The combination of doxorubicin/ifosfamide in the doses used by us is an effective but very hematotoxic regimen in STS and should be administered with G-CSF support. In our opinion, such a toxic chemotherapy should be considered in patients with metastatic STS only when additional therapeutic steps for selected patients are planned, such as metastasectomy or high-dose chemotherapy with peripheral blood stem cell s