The long-term therapeutic results achieved in a previous randomized study on stage IV Hodgkin's disease confirm the superiority of MOPP monthly alternated with ABVD compared to MOPP alone. To more closely meet the requirements of the Goldie and Coldman hypothesis, we activated a randomized study testing MOPP-ABVD through two different sequences in July 1982. One arm consisted of monthly alternating one cycle of MOPP and one cycle of ABVD; in the other arm, one half cycle of MOPP was alternated with one half cycle of ABVD within a one-month period (hybrid regimen). Each regimen was given to complete remission plus two consolidation cycles (minimum six cycles). After maximal tumor shrinkage, moderate doses of radiotherapy (25-30 Gy) were delivered to the lymphoid region(s) if bulky at the start of chemotherapy. A total of 300 patients with stage IB, IIA bulky, IIB, III (A + B) and IV Hodgkin's disease previously untreated with chemotherapy or failing after extensive irradiation were evaluated. At a median follow-up of five years, alternating and hybrid regimens yielded superimposable treatment outcomes: complete remission 89 versus 88%, freedom from first progression 65 versus 70%; relapse-free survival 72 versus 78%, overall survival 81 versus 80%, respectively. Tumor cell burden expressed as number of involved nodal sites and presence of pulmonary hilus involvement were the prognostic variables able to significantly influence treatment outcome. Conversely, stage, constitutional symptoms, and histology had no impact on the five-year results.(ABSTRACT TRUNCATED AT 250 WORDS)