Six monoclonal antibodies to proteins of Streptococcus pneumoniae were tested in a dot blot assay for reactivity with 499 clinical isolates of pneumococci. Forty-four percent of the isolates reacted with at least one of the antibodies. Nineteen patterns of reactivity were identified and each designated as a provisional protein serotype. Protein serotyping identified pneumococcal strains independently of their capsular type and made it possible to differentiate strains within most capsular types. A protein serotyping system provides a new dimension to the phenotypic identification of S. pneumoniae and may eventually provide a basis for assessing the population structure of these organisms. © 1988.