Interleukin-5 was initially characterized in murine systems, where it was found to have B-lymphocyte proliferative and differentiative activity and to promote the growth of eosinophils. Recombinant production of human IL-5 was soon accomplished by using murine IL-5 cDNA to isolate the highly homologous human sequence. Although human IL-5 was also found to be an eosinophil-active growth factor, a significant biologic effect of IL-5 on human B lymphocytes was initially difficult to demonstrate. More recently, reports from our own laboratory and other laboratories have provided evidence that IL-5 does have activity on human B lymphocytes and that human B lymphocytes may even produce IL-5 in some situations, suggesting the possibility of autocrine stimulatory mechanisms. However, we and others have failed to demonstrate the known heterodimeric high-affinity IL-5 receptor on human B lymphocytes, in spite of evidence that we have accumulated suggesting that human B lymphocytes specifically bind IL-5. We review our own work and that of others in an area that will remain controversial until a human B-lymphocyte IL-5 receptor is definitively identified and characterized.