Interleukin-5 plays a pivotal role in the regulation of Ig secretion from murine B cells. Resting B cells express few, if any, IL-5 receptors and do not respond to the lymphokine. Culture of resting B cells with IL-4 induced expression of the IL-5R alpha-chain, while signaling through membrane Ig stimulated expression of the IL-5R beta-chain. Surprisingly, IL-4 suppressed expression of the beta-chain on activated B cells and inhibited responsiveness to IL-5 in subsequent cultures. Simultaneous culture of B lymphoblasts with IL-4 and IL-5 elicited sustained expression of the beta-chain and promoted secretion of IgM. Thus, expression of IL-5 receptors and induction of Ig secretion requires coordination of signals provided by membrane Ig, IL-4, and IL-5.