Immune-mediated effects appear to play a major role in controlling minimal residual disease (MRD). We, therefore, investigated the role of recombinant human interleukin-2 (rIL-2) given concomitantly with interferon-alpha (IFN-alpha) in malignant lymphoma (ML) patients with responding disease following autologous bone marrow or blood stem cell transplantation (ABSCT). Fifty-six patients were included in this investigation. Thirty-two patients had non-Hodgkin's lymphoma (NHL) and 24 patients had Hodgkin's disease (HD). Sixty-one patients (NHL 36, HD 25) served as historical controls. Patients from both groups had similar demographic characteristics, the same stage of disease at presentation, status of disease at transplantation, conditioning regimens, and type of transplant. rIL-2 and IFN-alpha were self-administered in two cycles beginning 2.5 to 10.5 months (median, 4 months) posttransplant and separated by a 4-week interval. Each cycle consisted of IFN-alpha subcutaneously (SC) 3 x 10(6) U/d x 5 d/wk combined with rIL-2 SC 3 to 6 IU/m2/d x 5 d/wk for 4 weeks. The incidence of survival and disease-free survival (DFS) was significantly higher in the group under investigation than in the historical controls (P < .01). Of 56 patients with ML treated with IFN-alpha + rIL-2, 45 patients are DFS (80.4%) after a follow-up of 7 to 78 months (median, 34 months), whereas in the historical controls, 32 of 61 (52.5%) patients are disease free, in a follow-up of 4 to 84 months (median, 23 months) posttransplant (P < .01). Our preliminary results are encouraging and suggest that home administered immunotherapy with IFN-alpha and rIL-2 is relatively well tolerated and may intensify remission in ML patients with MRD following ABSCT.