Adherence of non-typable Haemophilus influenzae to respiratory epithelium was evaluated in a cotton rat model of respiratory syncytial virus (RSV) infection. Colonization with non-typable H. influenzae increased to a maximum within 4 days of RSV infection compared to RSV negative controls (4.58 +/- 0.17 vs 3.82 +/- 0.23 log colony forming units (CFU) per ml, P less than 0.05) and then declined over the subsequent 10 days (2.0 +/- 0 vs 3.78 +/- 0.39 CFU per ml, P less than 0.0001). In a second series of experiments, attachment of non-typable H. influenzae to epithelial cells collected from RSV infected cotton rats at the time of maximum virus replication was not different from controls (57.4 +/- 18.3 vs 52.0 +/- 24.3 bacteria per 50 cells). Systemic immunity to non-typable H. influenzae as measured by IgG-specific antibody to the outer membrane complex and bactericidal antibody did not influence colonization. These data suggest that colonization with non-typable H. influenzae is significantly affected by a concurrent infection with RSV; however, the site of bacterial attachment is not known.