One hundred and two patients with previously untreated Hodgkin's disease, stages IB through IIIB, were randomized within their pathological stage to receive total-lymphoid radiation, either alone or followed by six cycles of MOPP (nitrogen mustard, vincristine, procarbazine, and prednisone) therapy. The group receiving radiotherapy alone had 10 relapses, including 2 deaths from disease. The group assigned to sequential radiotherapy and chemotherapy had one relapse. The number of relapses in the group receiving sequential therapy (1/48) was significantly less than that in the group receiving radiotherapy alone (10/45; P < 0.01). The mean duration of follow-up from the end of MOPP chemotherapy in the 35 patients who completed sequential therapy was 375 days. The MOPP therapy was tolerated by patients who had recently received total-lymphoid radiation, and it significantly improved their probability of disease-free survival (P < 0.01). Actual survival was not significantly different for the two groups (P = 0.10).