Host development of human anti-mouse antibodies (HAMA) in response to administered antibodies has been reported as a problem for antibody imaging and therapy. However, radioimmunotherapy has been shown to be effective in patients with B-cell malignancies because their immunodeficient state precludes or delays development of a HAMA response to mouse antibodies. Baseline HAMA activity was assayed in 60 patients with B-lymphocytic non-Hodgkin's lymphoma or chronic lymphocytic leukemia and sequentially in 43 patients who were subsequently treated with radiolabeled Lym-1 antibody. Pre-existing "HAMA" activity was found in 3 (5%) of the 60 patients screened for treatment consideration. The incidence of development of HAMA in the 43 patients treated with multiple doses of radiolabeled Lym-1 antibody was 12 (28%). There was no evidence for an anaphylactoid or related response in the HAMA positive patients. HAMA activity interrupted therapy in 14% of the patients (6 of 43) but did not preclude therapeutic responses to radiolabeled Lym-1 therapy. Medial survival for the HAMA positive patients was longer (18 months) than for those who did not develop HAMA activity (9 months).