Human nasopharyngeal carriage of Streptococcus pneumoniae constitutes the major natural reservoir of pneumococci and is thought to be the prelude to virtually all pneumococcal disease. If carriage could be greatly reduced, pneumococcal transmission and disease could be largely eliminated. To facilitate the studies of mechanisms important in carriage and to identify immunogens that can elicit protection against carriage, we characterized an adult mouse model of nasopharyngeal carriage. Non-anaesthetized mice were inoculated intranasally with pneumococci in 10 μl of fluid. Nasopharyngeal carriage was observed with strains of capsular types 3, 4, 6A, 6B, 14, 19, and 23. Carriage was stable over time, and the numbers of pneumococci carried were relatively independent of inoculation dose; findings which indicate that the recovery of pneumococci from 1 day to 2 weeks post inoculation was dependent on colonization, rather than just temporary contamination. To ensure carriage in the largest percentage of mice, without causing sepsis or death, inoculations of 107 colony forming units (cfu) should be used. In this model, carriage was generally observed without concomitant bacteremia or sepsis and carriage was observed even with strains that were avirulent when injected i.v. The model should be useful for the identification of protection-eliciting antigens, since intranasal immunization with heat-killed pneumococci or lysates of pneumococci protected against carriage.