The role of IgG antibody in the sensitization of human basophils and mast cells to antigen is uncertain. To help resolve this uncertainty, we characterized by two-color fluorometric analysis the Fc receptors for IgG (Fc gamma R) on human basophils. Basophil-containing mononuclear cell fractions of atopic and nonatopic adult volunteers were incubated sequentially with fluorescein isothiocyanate-conjugated murine monoclonal IgE and biotinylated monoclonal antibodies (MAb) that bind specifically to the different Fc gamma R subtypes. Binding of biotinylated MAbs was visualized after subsequent incubation with phycoerythrin-strepavidin conjugate. Basophils did not react with a murine monomeric IgG2a, which binds specifically through its Fc to the high-affinity Fc gamma RI (CD64), or with MAbs specific for the low-affinity Fc gamma RIII (CD16). However, basophils reacted with a MAb specific for the low-affinity Fc gamma RII (CDw32). The profile of basophil Fc gamma R expression was not altered after brief IgE-mediated activation. In addition, pretreatment with gamma interferon, which induced expression of Fc gamma RI (CD64) on neutrophils, did not induce Fc gamma RI expression on basophils. These results indicate that the Fc gamma R present on basophils is exclusively of the Fc gamma RII (CDw32) subtype. The absence of the high-affinity Fc gamma RI (CD64) suggests that antigenic sensitization of basophils by monomeric IgG does not occur.