Clinical and bacterial findings were prospectively studied in 90 children hospitalized because of middle or lower respiratory tract infection caused by respiratory syncytial virus (RSV) during a surveillance period of 12 months. The results were compared with those of RSV-negative children hospitalized with identical indications during the 3 peak months of the RSV epidemic (N = 91) or for the 3 months after the outbreak (N = 99). A high frequency of pneumonia and acute otitis media were found in both RSV-positive and RSV-negative children during the epidemic, but not in control patients after the epidemic. Bacterial infection, based on a significant rise of antibody titer and/or on detection of pneumococcal antigen in serum or urine, was observed in 39% of the children with RSV infection. The respective figures were 24% in RSV-negative children hospitalized during the epidemic and 8% after the epidemic. Our observations stress the role of RSV as a predisposing agent for secondary bacterial infection in the airways of children. The most common bacteria involved in the mixed RSV-bacterial infections were Streptococcus pneumoniae and Haemophilus influenzae, the latter being found only in pneumonic patients. The presence or absence of pneumonia or acute otitis media was not significantly correlated with evidence of pneumococcal infection. We conclude that a bacterial pathogen should be actively sought when managing patients with lower respiratory tract syndromes, especially in those who have evidence of RSV infection.