Forty-seven patients with advanced Hodgkin's disease were entered in a prospective, randomized trial comparing MOPP (mechlorethamine, vincristine, procarbazine, and prednisone) with a regimen containing lomustine (CCNU), vinblastine, and prednisone (CCNU-VP). Both groups were comparable for the variables of age, stage, substage (symptoms), histology, prior radiation, and sites of involvement. Seventy-two percent of CCNU-VP-treated patients achieved a pathologically documented complete remission (CR) compared to 41% of the MOPP-treated group. Two additional patients treated with MOPP had remission documented only clinically but have been long-term, disease-free survivors. There was a greater frequency of CR in the patients who had received previous irradiation when compared to patients with no prior irradiation. After a median follow-up of greater than 89 months, there is no statistical difference between the two treatment groups in survival (45% for MOPP and 60% for CCNU-VP). Further, no statistical difference in survival for the two treatment groups was noted when compared by histology, stage, or symptoms. The CCNU-VP combination was better tolerated with significantly less nausea and emesis. The alternative drug regimen of CCNU-VP appears to be as effective as MOPP in producing CR and long-term survival in patients with advanced Hodgkin's disease.