Interleukin 5 (IL5) acts on eosinophil differentiation and activation, suggesting the existence of a membrane receptor for IL5 on eosinophils. Here, we report that 125I-labeled recombinant human 11,5 bound, at 4°C, to high affinity receptors on human eosinophils. The association constant was higher for hypodense eosinophils (1.93 × 109 M−1) than for normodense cells (0.39 × 109 M−1), with a closely related number of receptor sites per cell. No specific binding occurred on neutrophils. The specific binding of 1165 was induced by overnight incubation at 37°C of human eosinophils with granulocyte/macrophage (GM)-CSF. The levels of increase were significantly higher for normodense than for hypodense eosinophils, suggesting a previous in vivo activation of the later subpopulation by GM-CSF 1173 was ineffective by itself but synergistically enhanced the effect of GM-CSF. Specificity studies showed that the binding of 125I-labeled IL5 was inhibited by 116, but not by other cytokines, on human eosinophils. These results show the existence of a specific binding site for IL5 on human eosinophils with a variable affinity on eosinophil hypodense or normodense subpopulations, as previously reported for other membrane receptors. © 1990, Rockefeller University Press., All rights reserved.