Pneumococcal diseases such as otitis media, pneumonia, and meningitis are invariably preceded by nasopharyngeal colonization, and herd immunity against pneumococcal disease requires protection against colonization. An early study in mice demonstrated that mucosal immunization with cholera toxin B subunit as adjuvant could elicit solid mucosal immunity. Recent data from several laboratories provides support for three different mechanisms by which adaptive immunity can provide protection against colonization. (1) IL-17-dependent T cell immunity can recruit PMN to sites of colonization. This IL-17-dependent immunity can be elicited by immunization with antigen plus a mucosal adjuvant, or can be elicited by colonization itself. (2) Immunity against colonization can be mediated by mucosal IgA and at the mucosal surface passive mucosal IgA antibody provides much better protection against carriage than passive IgG antibody. (3) Complement-fixing IgG antibody can protect against colonization and may act by protecting against colonization of bacteria. Copyright © 2011 S. Karger AG, Basel.