The immunoglobulin nature of isoantibodies combining wtih human cell cultures was investigated. The sera tested in this study originated from 3 patients who recieved multiple blood transfusions, 3 multiparous women and 1 patient after surgical removal of a rejected kidney homograft. The following evidence was presented for the IgG [immunoglobulin G] nature of isoantibodies under investigation. Mixed agglutination tests were positive in using an erythrocyte indicator with anti-IgG antibodies but not in using an indicator with anti-IgM [immunoglobulin M] antibodies. Upon separation of an isoantibody-containing serum, the serologic activity was recovered in the IgG but not in the IgM fraction. Eluates recovered from cell cultures sensitized by isoantibodies had antigenic properties of IgG but not of other immuno-globulins.