In a multicenter study 46 untreated patients with highly-malignant non-Hodgkin's lymphomas stage II-IV received 6 courses of the following drug combination: cyclophosphamide 750 mg/m2 i.v. day 1, adriamycin 50 mg/m2 i.v. day 1, vincristine 2 mg i.v. day 1, prednisolone 100 mg p.o. days 1-5, and etoposide 100 mg/m2 i.v. days 3-5. Between courses 4 and 5 an involved field irradiation with a total dose of 25 Gy was employed. The overall response rate was 91%, with 38 patients achieving a complete remission (82%), 4 patients achieving a partial remission (9%), and 4 patients showing no response (9%). During a median follow-up period of 34 months 16 out of 38 patients relapsed, 4 of them achieving a second complete remission with the same drug regimen. A maintained complete remission up to 52 months was seen in 51% of all patients initially achieving CR. The overall survival curve shows a plateau at 60% at 30 months, while disease-free survival shows a plateau at 51% at 36 months. Mean side effects of this drug regimen were alopecia (89%), nausea/vomiting (76%), and leukopenia (61%). No therapy-related deaths were reported. The results of this study demonstrate that this treatment produces high complete remission rates and that the majority of these patients achieves long-term disease-free survival.