Cytokines play an important role in the regulation of both normal and malignant B cells. In this paper we give a brief overview of the major cytokines involved in the regulation of B-CLL proliferation.In vitroexperiments have indicated that there is an antagonistic interaction between TNF-αas a growth-enhancing factor and IL-4, which inhibits the growth of B-CLL. We have extended these findings with recent experiments on the intracellular signals which might be involved in these processes. We show that increased levels of intracellular cAMP dose-dependently inhibit the TNF-α-induced proliferation of B-CLL. On the basis of these results, we propose a model for the signals involved in the regulation of B-CLL proliferation. The implications for possible new ways of treatment are discussed.