- Background: We compared the clinical and demographic features of children with lower respiratory tract infection (LRI) caused by human metapneumovirus (HMPV), respiratory syncytial virus (RSV) and influenza A virus and sought to determine whether coinfection by HMPV and other respiratory viruses leads to increased disease severity. Methods: Nasal wash specimens were prospectively obtained from 516 children hospitalized for LRI during a 1-year period and tested for the presence of HMPV by reverse transcription-polymerase chain reaction and for RSV and influenza A by direct immunofluorescence. Results: HMPV was detected in 68 (13%) patients and was the third most common viral pathogen; 16 of 68 HMPV-positive children (24%) had coinfection with other respiratory viruses (HMPVco). HMPV patients were older than RSV patients (17.6 ± 16.8 months versus 10.5 ± 11.8 months, P = 0.02). HMPV was associated with wheezing and hypoxemia at a rate similar to that of RSV and higher than that of influenza A. Atelectasis was more common among HMPV (40%) than among RSV and influenza patients (13%, P < 0.05 for each). HMPV infection was more often associated with a diagnosis of pneumonia than RSV and influenza A and was more often associated with a diagnosis of asthma and less often associated with a diagnosis of bronchiolitis than RSV infection (P < 0.05 for each), even when corrected for age. Children with HMPVco had a higher rate of gastrointestinal symptoms but did not show a more severe respiratory picture. Conclusions: The clinical pattern of HMPV more closely resembles that of RSV than that of influenza A LRI, yet the differences in age, radiographic findings and clinical diagnosis suggest that HMPV pathogenesis may differ from that of RSV.