Resting B cells express few, if any, receptors for interleukin-2 (IL-2), whereas activated B cells can express receptors for and respond to IL-2. IL-2 receptors can exist on the cell surface in three different forms; the complete high-affinity receptor, a heterodimer consisting of a chain of relative molecular mass (Mr) 70-75,000 (70-75K) and a chain of Mr 55K; the 70-75K chain alone, with intermediate affinity for IL-2; or the 55K chain alone, with low affinity for IL-2. We have previously reported that IL-5-stimulated B cells are induced to express the 55K chain. We report here evidence for the differential regulation of the expression of the two chains, namely that IL-4 and IL-5 can independently induce expression of the 70-75K and 55K chains respectively on murine B cells. As expected, cells stimulated to express the 55K chain alone are unresponsive to IL-2, whereas cells stimulated to express either the 70-75K chain or the 70-75/55K heterodimer respond to IL-2, at a high and low ligand concentration respectively, with a marked increase in proliferation. This orchestration of receptor expression and factor responsiveness may represent a novel activation pathway for B cells, where the two chains of a compound receptor are shown to be independently regulated.