No consistent effect on nasal carriage rates of Streptococcus pneumoniae belonging to vaccine types was observed during a randomized, controlled trial of a 14-valent pneumococcal vaccine, which included 1273 Australian children aged 6 to 54 months. Nasal carriage of S pneumoniae was associated with a significantly elevated homotypic serum antibody concentration for types 18C, 19F, and 23F, but not for types 6A and 14 (these five types are the most important causes of pneumococcal infections in children). Upper respiratory tract carriage seems to play an important role in natural acquisition of antibody to some but not all pneumococcal serotypes. These findings help to explain why pneumococcal vaccine fails to protect young children from acute otitis media.