To characterize the Fc receptors on rat alveolar and peritoneal macrophages (M phi), we analyzed their ability to form rosettes with fixed ox erythrocytes (Eo') coated with myeloma proteins of all rat Ig classes and with fresh erythrocytes (Eo) sensitized with rat IgG1 and IgG2, rabbit IgG and IgM, and mouse IgA antibodies. The M phi formed rosettes with Eo' coated with rat myeloma proteins of classes IgG1, IgG2a, IgG2b, and IgE but not IgG2c, IgA, IgM, and IgD. Rat M phi also formed rosettes with Eo' coated with human IgG1, IgG3, IgG4, mouse IgG1, IgG2a, IgG2b, and rabbit IgG. Furthermore, rat M phi formed rosettes with Eo sensitized with rat IgG1, IgG2, or rabbit IgG antibodies but not with Eo sensitized with rabbit IgM or mouse IgA antibodies. Trypsin treatment of rat M phi abolished IgG1/IgG2b and IgE but not IgG2a rosettes. The IgG2a and IgE rosettes were Ig class specific because they were inhibited only by rat IgG2a and rat IgE, respectively. In contrast, IgG1 and IgG2b rosettes were inhibited equally by IgG1 and IgG2b. Heterologous IgG inhibited IgG1/IgG2b but not IgG2a rosettes. Rat IgE inhibited rat IgG1, IgG2b, and heterologous IgG rosette formation on rat M phi. Although Eo' coated with rat IgE formed rosettes with mouse P388D1 macrophagelike cells, rat IgE did not inhibit IgG rosettes on these cells. Similarly, Eo' coated with human IgE formed rosettes with human U937 macrophage-like cells, but human IgE did not inhibit IgG rosettes on these cells. The results indicate that rat M phi have at least three distinct Fc receptors: one is specific for rat IgG2a and is trypsin resistant; a second is specific for rat IgE and is trypsin sensitive; and a third reacts with rat IgG1 rat IgG2b, and heterologous IgG and is trypsin sensitive. Rat IgE inhibited IgG1/IgG2b rosettes undirectionally and uniquely on rat M phi.