Mycoplasma pneumoniae accounts for up to 35% of all pneumonias at times when influenza epidemics are not prevalent. Therefore, considerable efforts have been directed towards the developmemt of a vaccine against mycoplasmal respiratory tract disease. The protective efficacy of inactivated M. pneumoniae vaccine, prepared so far, did not exceed 67%. This incomplete protective effect may have been due to insufficient immunogenicity and/or to failure of vaccines administered by the parenteral route to stimulate local immune mechanisms on the mucosal surfaces of the respiratory tract. Intranasal inoculation of attenuated strains, either of high passage level on artificial medium or temperature-sensitive mutants, were therefore tested as vaccine candidates for M. pneumoniae disease, but the attenuation for man, achieved so far, was not sufficient. Therefore, the successful development of polysaccharide vaccines for pneumococcal and meningococcal diseases stimulated a study on similar approaches for the development of the prophylaxis for mycoplasma pneumonia. The immunogenicity and the protective efficacy of M. pneumoniae polysaccharides and glycolipids were investigated in hamsters. Staphylococcal radioimmunoassay antibodies could be detected in the sera of the animals after intramuscular injection of M. pneumoniae polysaccharides. A significant reduction in the lung lesion score and in the number of viable organisms in the lung was observed in animals immunized with polysaccharides by the intramuscular or intranasal route, 10 d after challenge with virulent organisms. A protective effect was not seen in animals previously immunized with reaggregates of M. pneumoniae glycolipids and membrane protein of Acholeplasma laidlawii, although serum antibodies could be detected prior to challenge. The results encourage the continuation of experiments on polysaccharides as vaccines against mycoplasmal pneumonia.