B cells from patients suffering from B-type chronic lymphocytic leukemia (B-CLL) are susceptible to the effects of several interleukins. Using the cells from 12 different patients we show that IL-4 does not synergize with anti-mu antibody for the enhancement of DNA synthesis. Moreover IL-4 profoundly (90%) suppresses the response to IL-2 in the 10 patient responders to this interleukin. This suppression occurs whether IL-2 is used alone, in costimulation with anti-mu antibody, or in synergy with IFN-gamma. In no instance did IL-4 induce terminal differentiation. This negative effect of IL-4 can take place in monoclonal B-CLL cells where IL-4 enhances the expression of CD23. IL-4 does not interfere with the upregulation of CD25 by IL-2. Thus, IL-4 may display inhibitory effects on the proliferative response of selected B cell populations. The antagonism between IL-4 and IL-2 has important implications for the potential use of cytokines in the management of B-CLL patients.