3H-thymidine incorporation following stimulation with interferon (IFN) in vitro was investigated in cell cultures from peripheral blood of patients with chronic lymphocytic leukemia (CLL), spleens from necro-kidney transplants and healthy blood donors. It was demonstrated, that IFN can induce a proliferative response in some normal as well as leukemic B lymphocyte subsets. The responses were not T-cell dependent. The results indicate, that B-cell subsets that proliferate in the presence of IFN, are present in higher proportions in spleen than in peripheral blood, and that they constitute a portion of the leukemic blood lymphocyte pool in some patients with CLL. We have previously demonstrated, that IFN induces varying degrees of transformation and differentiation in blood lymphocytes from a majority of CLL patients. The functional characteristics of different B-cell subsets, and their heterogeneous distribution in leukemia, may be important for the results of IFN treatment in various malignant B-cell disorders.