In a prospective multicenter trial the efficiency of the response-adapted COP-BLAM/IMVP-16 protocol to induce complete remissions (CR) in high-grade malignant non-Hodgkin's lymphomas as well as the prognostic relevance of adjuvant radiotherapy were investigated. From 1986-1989, 548 patients (median age 56 years) with stage II-IV (Ann Arbor) disease were treated with five cycles of COP-BLAM followed by two cycles of IMVP-16. If only a partial remission was obtained at the time of first restaging (RS) after three cycles (delayed response), treatment was switched to IMVP-16 (two to five courses) immediately. Patients achieving CR by the second RS after chemotherapy were randomized to adjuvant radiotherapy or observation. Responses to chemotherapy were 63% CR in patients completing the second RS (N = 350) or 72% if patients achieving late CR by consolidating radiotherapy are added; responses were 58% or 65% if all deaths prior to the second RS are included (N = 50). Overall and relapse-free survival were 71% and 68% at one year and 63% and 61% at two years. Multivariate risk factor analysis proved the early (by first RS) CR response to possess predominant prognostic relevance for survival. A significant advantage of adjuvant radiotherapy over no further treatment for duration of CR is not yet discernible. These results emphasize the importance of a rapidly achieved CR, thus contributing to the design of future trials.