Two fowl antisera to plyclonal human IgG and one to a mouse IgG1 myeloma protein, after absorption either with homologous F(ab)2 alone, or also with myeloma proteins of known subclasses, cross-reacted in immunoelectrophoresis or immunodiffision withthe IgG of many mammalian species. Often more than one IgG precipitation line was formed in the corss-reacting systems. By testing isolated IgG1 and IgG2 fractions from mouse, rat, guinea-pig, bovine and dog sera, it was shown that the distinct arcs seen with whole serum corresponded to the known IgG subclasses of these species. With rabbit serum as antigen, the two anti-human-Fc sera diffusing from neighboring wells formed a 'spur', showing that they were reacting with determinants on different molecules, and that therefore rabbit IgG contains two antigenically distinct Fcpopulations. With the possible exception of canine IgG1 and human IgG4, no antigenic homologies were found between the subclasses of different species, thus supportingthe view obtained from sequence data, namely that IgG subclasses within species havearisen independently