The Ann Arbor staging classification has proven less useful in nonHodgkin's lymphoma, because this malignancy is inherently a multifocal disorder. Since 1985, 57 adult patients with advanced B-lymphocytic malignancies that progressed despite standard therapy entered into one of three different therapy trials using radiolabeled Lym-1 antibody. Tumor regression in 31 (54%) of these patients fulfilled conventional requirements for an oncological response to the therapy. To define the role of radioimmunotherapy in B-lymphocytic malignancies better and to find opportunities for improving its therapeutic efficacy, the records of these patients were reviewed to assess the significance of various parameters as prognostic indicators. Twenty-one pretherapy characteristics were evaluated, including age at diagnosis, age at study entry, sex, Karnofsky performance status, prior chemotherapy and radiation therapy, interval since diagnosis, histology, constitutional B symptoms, extranodal malignancy (excluding marrow), bone marrow malignancy, tumor bulk, and circulating malignant cells; blood tests included lymphocyte, granulocyte, platelet, hematocrit, serum lactate dehydrogenase (LDH), interleukin 2 receptor, and human antimouse antibody levels. In the multivariate analysis, LDH and Karnofsky performance status were the parameters that best predicted survival, complete and partial remission, and time to progression; interleukin 2 receptor and LDH best predicted complete remission. These prognostic factors for radioimmunotherapy outcome are consistent with the pretherapy characteristics observed to be significant for chemotherapy.