BALB/c mice made antibody against an allotype determinant of C57 immunoglobulin after only three injections of non-agglutinated serum. Evidence was obtained indicating that the determinant was carried by the γG2a globulin class. C3H and CBA mice did not produce anti-allotype antibody when submitted to the injection schedule to which BALB/c animals responded. The results of treating F1 and backcross mice demonstrated that the strain difference was under polygenic control.