Previous studies have suggested that sera from animals immunized with whole Streptococcus mutans cells may cross-react with human and monkey heart sarcolemmal tissues. In the present study, sera and saliva from rats and rabbits immunized peripherally with ribosomal preparations from S. mutans 6715 (serotype g) or GS-5 (serotype c) were examined for their ability to react with normal human heart sarcolemmal and kidney glomerular tissues by using enzyme-linked immunosorbent and immunofluorescence assays. The results showed that antibodies to serotype g and c ribosomal preparations do not react with either the human heart or renal antigens. Sera from mice immunized with human heart tissue and from a patient with a high anti-streptolysin O titer reacted strongly with human heart sarcolemmal and kidney glomerular tissues. These data indicated that ribosomal preparations from S. mutans lack the putative human heart cross-reactive determinant and suggest that the use of an S. mutans ribosomal vaccine against dental caries may not be pathogenic to human heart or renal tissues.