The clinical impact of human metapneumovirus (hMPV) genotypes and the relation between the hMPV genotype in circulation and genotypespecific seroprevalence are yet to be clarified. We determined the genotypes of 93 hMPV strains that were isolated between 2004 and 2006 in Yamagata, Japan, and identified 35 genotype A2, 14 genotype B1, and 44 genotype B2 isolates. Children infected with genotype A2 hMPV were significantly older than those infected with genotype B1 hMPV. Diagnosis of laryngitis was more common in children with genotype B1 hMPV infection and wheezing was more prevalent in children with genotype B1 and B2 hMPV infection than in those with genotype A2 hMPV infection. We then examined genotype-specific seroprevalence by neutralization assay. The higher seropositive rate for the B2 genotype among the children aged 1-2 years is likely to reflect the outbreak of B2 genotype strains in the previous year in this community. The low seropositive rate for the B1 genotype among children aged 1-2 years appears to be associated with a finding that more than 70% of children infected with the B1 genotype were less than 3 years old. In conclusion, we found that the different clinical characteristics of hMPV infection may be associated with hMPV genotype, and the predominant genotype during a season and the affecting age may be closely related to genotype-specific immune status within a community. J.Med. Virol. 80:1084-1089, 2008. © 2008 Wiley-Liss, Inc.