In a multicentre phase III trial 105 previously untreated patients with high-grade non-Hodgkin’s lymphomas stage II-IV were randomized to receive either 4 cycles of CHOEP (cyclophosphamide 750 mg/m2 i.v. day 1, doxorubicin 50 mg/m2 i.v. day 1, vincristine 2 mg i.v. day 1, etoposide 100 mg/m2 i.v. days 3–5, prednisolone 100 mg p.o. days 1–5) (treatment arm A), or 4 cycles of chemotherapy with hCHOP (cyclophosphamide 1,200 mg/m2 i.v. day 1, doxorubicin 40 mg/m2 i.v. days 1+2, vincristine 2mg i.v. day 1, prednisolone 100mg p.o. days 1–5) alternating with IVEP (ifosfamide 1,500 mg/m2 i.v. days 1–5, vindesine 3 mg/m2 i.v. day 1, etoposide 120 mg/m2 i.v. days 3–5, prednisolone 100 mg p.o. days 1–5) in treatment arm B. After 4 cycles of chemotherapy an involved field irradiation with a total dose of 35 Gy was given to all patients demonstrated to be in complete or partial remission without persisting extranodal disease. A complete response (CR) was seen in 86/105 patients (82%) with 88% CR in arm A vs. 76% CR in arm B. During a median follow-up of 11 months (range 2–31 months) 13 patients relapsed (6 patients arm A, 7 patients arm B). The overall survival at 30 months is projected to be 72% vs. 83% for arm A and B respectively. Disease-free survival is projected to be 78% in arm A and 45% in arm B at 28 months. So far, the differences in CR, survival and disease-free survival are not statistically significant. Toxicity of all regimens was acceptable, however, with a significant morbidity and 1 treatment-related death in patients > 70 years after hCHOP. Main side effects were mild nausea/vomiting, leukopenia and fever/infection associated with leukopenia. In conclusion, both treatment modalities produced high complete remission rates. A longer follow-up will be needed to exclude differences in overall and diseas