Factors that may account for the susceptibility of certain individuals to rheumatic heart disease will be studied. An abnormality in the capacity of tissue infected by the group A streptococcus to degrade streptococcal cell components will be investigated. Degradation of the streptococcal polysaccharide and peptidoglycans by tissue macrophages will be examined in rheumatic and non-rheumatic tissues. In addition, the role of cell-mediated immunity in the pathogenesis of rheumatic carditis and valvulitis will be studied further using an experimental model. Cardiac tissue from experimental animals will be cultured in vitro. Cytotoxicity of serum or lymphocytes from animals immunized with group A streptococci to these target cells will be determined.