It has been proposed that the relative scarcity of Staphylococcus aureus and Streptococcus pneumoniae cocolonization in the nasopharynxes of humans can be attributed to hydrogen peroxide-mediated interference competition. Previously it has been shown in vitro that H(2)O(2) produced by S. pneumoniae is bactericidal to S. aureus. To ascertain whether H(2)O(2) has this inhibitory effect in the nasal passages of neonatal rats, colonization experiments were performed with S. aureus and S. pneumoniae. The results of these experiments with neonatal rats are inconsistent with the hypothesis that hydrogen peroxide-mediated killing of S. aureus by S. pneumoniae is responsible for the relative scarcity of cocolonization by these bacteria. In mixed-inoculum colonization experiments and experiments where S. aureus invaded the nasopharynxes of rats with established S. pneumoniae populations, the density of S. aureus did not differ whether the S. pneumoniae strain was H(2)O(2) secreting or non-H(2)O(2) secreting (SpxB). Moreover, the advantage of catalase production by S. aureus in competition with a non-catalase-producing strain (KatA) during nasal colonization was no greater in the presence of H(2)O(2)-producing S. pneumoniae than in the presence of non-H(2)O(2)-producing S. pneumoniae.