In a multicenter prospective randomized therapeutic trial in advanced (stage II-IV disease, Ann Arbor classification) high-grade malignant non-Hodgkin's lymphomas (NHL, Kiel classification) a sequential combination of the COP-BLAM (5 cycles) and the IMVP-16 (2 cycles) protocols was employed. Response was first determined after 2-3 cycles. In a response-adapted manner the therapy was immediately switched to IMVP-16 if only a partial remission or no response was obtained as evidenced by the first restaging. The aim of the study is the investigation of the efficiency of this concept to induce stable remissions. In an additional randomized trial, involving all patients reaching complete remissions after chemotherapy (second restaging), the prognostic relevance of adjuvant radiotherapy as compared to therapy-free follow-up is evaluated. Eighty percent of the 191 recruited qualified patients have so far become evaluable. Complete clinical remissions were achieved in 76/148 (51%) of the patients up to the first, in 52/85 (61%) of the patients up to the second restaging. Only in a few cases did the expected toxicity of intensive polychemotherapy reach WHO grade 3-4, including nausea and diarrhea, infections, septic complications, myelotoxicity, and stomatitis. Four of the 29 deaths recorded so far occurred in complete remission due to treatment-related complications, whereas 22/29 (76%) died in progression and 3 of unrelated causes.