Skin sensitizing capacities of five groups of mouse immunoglobulin were investigated. Mouse 7 S γ2-globulins were capable of sensitizing guinea pig (heterologous) skin for passive cutaneous anaphylaxis and reverse passive cutaneous anaphylaxis. No heterologous passive cutaneous anaphylaxis activity was present, however, in the 7 S γ1-globulin, β2A-globulin or γ1-macroglobulin classes. The heterologous skin sensitizing ability of the 7 S γ2-globulins was further investigated by examining two subclasses, 7 S γ2a-globulin and 7 S γ2b-globulin, with the aid of purified mouse myeloma proteins. Heterologous skin sensitizing activity was identified in the γ2a-globulin but not in the γ2b-globulin subclass. The presence or absence of heterologous skin sensitizing activity within the 7 S γ2-globulin class correlated with the presence or absence of allotypic isoantigens and with specific antigenic determinants detected by rabbit antiserum.