S-carboxymethylcysteine (S-CMC) is a mucolytic agent that can prevent respiratory infection by decreasing the attachment of respiratory pathogens to human pharyngeal epithelial cells (HPECs). Streptococcus pneumoniae is a major cause of respiratory infections. A previous study revealed that treatment of S. pneumoniae with S-CMC caused a decrease in the attachment of this bacterium to HPECs. In the present study we found that the effect of S-CMC varied according to hosts and strains. S-CMC treatment altered the surface structure of S. pneumoniae, resulting in a decrease of attachment, without affecting the virulence of the bacteria. © 2008 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases.