This study evaluated the overall impact of human metapneumovirus (hMPV) infection in 1,505 children and their households, and compared it with infections due to respiratory syncytial virus (RSV) and influenza viruses. Nasopharyngeal swabs were used at enrollment to collect specimens for the detection of hMPV, RSV, and influenza virus RNA by reverse-transcriptase polymerase chain reaction (RT-PCR). hMPV was detected in 42 children (2.8%), RSV in 143 (9.5%; P < 0.0001 vs. hMPV), and influenza viruses in 230 (15.3%; P < 0.0001 vs. hMPV). Of the 42 hMPV-positive samples, one was also positive for RSV and six for influenza viruses, for a co-infection rate of 16.7%. Clinically, hMPV was identified only in patients with acute respiratory infection, whereas RSV and influenza viruses were also detected in patients with different clinical manifestations. Symptoms with statistically significant different proportions at presentation were fever (more frequent in the hMPV- and influenza-positive children) and wheezing with bronchiolitis or asthma exacerbation (more frequent among hMPV- and RSV-positive cases). The households of the hMPV- and the influenza-positive children had significantly more illnesses, needed significantly more medical visits, received more antipyretics, and missed significantly more work or school days than those of the RSV-positive children. Results show that hMPV is an emerging cause of acute respiratory infection in childhood, and may have a significant clinical and socioeconomic impact on children and their families. J. Med. Virol. 75:101–104, 2005. © 2005 Wiley-Liss, Inc.