Because of the ability of interleukin-2 (IL-2) to support the proliferation and activation of numerous types of immunocompetent cells and to support the survival of adoptively transferred lymphocytes, there has been considerable interest in its use in the immunotherapy of malignancies. While studies to date have indicated that IL-2 has activity against some malignancies, considerable toxicity has also been observed. Careful prescreening and selection of patients and appropriate management of toxicity can minimize adverse outcomes. Studies of IL-2 effects have provided intriguing evidence of interactions of the immune/cytokine system with the neuroendocrine, cardiovascular, and other systems. Studies in animal models have demonstrated the central role of an intact immune system in mediating many toxicities of IL-2. Several adverse effects of IL-2 appear to be mediated by other cytokines whose production is induced by IL-2. Studies into the pathogenesis and manifestations of IL-2 toxicity have offered the hope of developing less toxic approaches to IL-2 therapy. Several lessons from the IL-2 experience are likely to be applicable in the clinical development of other cytokines.