A high proportion of rabbits immunized with pooled rabbit heart homogenates in complete Freund's adjuvant responded with the production of multiple precipitating antibodies to soluble rabbit heart antigens. The most potent antisera revealed at least five distinct antigens. 2. Rabbit anti-rabbit heart antibodies reacted with similar antigens in other mammalian hearts, (human, rat, guinea pig, and bovine) with apparent "reactions of identity" by immunodiffusion. 3. Rabbits immunized with human, rat, or guinea pig heart homogenates also responded with multiple precipitating antibodies directed against rabbit cardiac antigens, although somewhat less intensively than animals immunized homologously. The specificities of these antibodies appeared to be the same as those evoked homologously. 4. The autoantibody nature of the homologously and heterologously induced responses was unequivocally demonstrated in several instances by reactions between the sera from immunized rabbits and their own hearts. 5. Many of the autoantibodies appeared to be directed against antigens restricted to the heart, judging by comparative immunodiffusion tests with other rabbit tissue extracts. This was convincingly confirmed by multiple absorption of potent antisera with several rabbit tissues. The cardiac-restricted antigens were also present in heart extracts of other mammalian species. In those instances where some of the cardiac-evoked autoantibodies reacted with other rabbit tissues, the tissue cross-reactions were quite variable. 6. Rabbits immunized with guinea pig heart homogenate suffered a high early mortality of undetermined cause, compared to animals immunized with rabbit, human, or rat hearts. 7. A small proportion of the anti-heart sera revealed immunodiffusion reactions with Group A streptococcal products, derived from organisms grown in antigen-free media. In these few instances, the reactions appeared unrelated to cardiac autoantibody responses.
