Maturation of B cells into immunoglobulin (Ig)-secreting cells is influenced by antigen-nonspecific growth and differentiation factors. In the present study, we have analyzed the effect of several recombinant cytokines (rIL2, rIFN-alpha, rIFN-gamma) on the terminal differentiation of B cells from 10 patients with chronic lymphocytic leukemia (CLL) stimulated with three different B cell activators (phorbolester TPA, staphylococcus aureus Cowan I bacteria, or pokeweed mitogen). Secretion of IgM, as determined by heavy-chain specific ELISA, varied widely among different CLL cell populations, but was induced in all cases by one or several of these activators. Importantly, this response was enhanced 2-10-fold in all patients by at least one of the tested recombinant cytokines alone, or a combination of rIL2 with rIFN-alpha or rIFN-gamma. The results illustrate the clonal heterogeneity of CLL B cell maturation in vitro and demonstrate that rIL2, rIFN-alpha or rIFN-gamma can act as a B cell differentiation factor, depending on the responsiveness (stage of differentiation) of the individual clonal B cell population.