T lymphocytes present in allergically inflamed tissue synthesize and secrete the cytokines interleukin (IL)-3, IL-4, IL-5, and granulocyte/macrophage colony-stimulating factor (GM-CSF). IL-3, IL-5, and GM-CSF, but also IL-4, may act as a chemotaxin on eosinophils. In contrast to the former cytokines, IL-4 is only chemotactic for eosinophils from the peripheral blood of patients with atopic dermatitis and not for eosinophils from normal individuals. IL-4 has the same chemotactic potency as the other cytokines. The optimal chemotactic potency is reached at a concentration of 10 nM. In contrast, neutrophils do not respond chemotactically to IL-4. Checkerboard analysis, inhibition studies with monoclonal anti-IL-4 antibodies, and desensitization experiments indicated specific interaction of IL-4 with eosinophils. In eosinophils from normal individuals, IL-4 responsiveness could be induced by pretreatment of the cells with IL-5 and GM-CSF. In addition to the fact that IL-4 may be responsible for selective eosinophil transendothelial migration, IL-4 may exert an important modulatory mode of action on eosinophil migration and function within allergically inflamed tissue. Our findings suggest the presence of a functional IL-4R on eosinophils from atopic dermatitis patients.