Background: Blood eosinophils have mRNA for FcγRIIIB (CD16) but no or minimal spontaneous CD16 expression. Because IFN-γ and chemotactic factors induce eosinophil CD16 expression in vitro, we postulated that blood eosinophils could express CD16. Objective: Blood of nonallergic controls and subjects with allergic rhinitis, allergic and nonallergic asthma, or hypereosinophilia of various etiologies were analyzed for leukocyte CD16 surface expression. Methods: CD16⁺ eosinophils were identified on the basis of physico-optic characteristics, major basic protein, CD49b expression, and sorting by flow cytometry and microscope examination. Results: Subjects with allergic rhinitis and subjects with asthma had higher median percentages of CD16⁺ eosinophils (8.1% [1% to 48.6%] and 7.3% [1.4% to 31.1%], respectively) than nonallergic controls and nonallergic asthmatics (3% [0% to 11%] and 4.6% [2.9% to 5.1%], respectively). In subjects with hypereosinophilia, CD16⁺ eosinophils were increased only in a case of drug allergy. When subjects with mild allergic asthma were challenged with a relevant aeroallergen, blood CD16⁺ eosinophils further increased during or after the late-phase response (6 to 48 hours after challenge; mean ± SEM, 9.4% ± 2.5% to 20.0% ± 3.0%). CD16⁺ eosinophils expressed more IL-5 receptor but less CD11b and IL-12p35 than did CD16⁻ eosinophils. Conclusion: Upregulation of blood CD16⁺ eosinophils in allergic conditions and its association with a modified phenotype suggest that CD16 receptor could play a role in eosinophil activation in allergy. (J Allergy Clin Immunol 2002;109:463-9.)