BACKGROUND: Human metapneumovirus (HMPV) is a recently discovered human paramyxovirus associated with a spectrum of respiratory symptoms from the common cold to pneumonia and bronchiolitis. OBJECTIVES: To assess the clinical significance and epidemiology of HMPV, standardized comparison of frequencies of infection, age profiles and disease associations were made with other respiratory viruses in Scotland. STUDY DESIGN: 7091 respiratory samples collected in Scotland between 1 July 2006 and 30 June 2008 from 4282 individuals were screened by multiplex RT-PCR for respiratory syncytial virus (HRSV), adenovirus (AdV), parainfluenza viruses 1-3 (PIV-1, -2 and -3), influenza A and B and by nested RT-PCR for HMPV. RESULTS: HMPV was the fifth most prevalent virus (2.0% of samples), found predominantly in young children in winter months. In the 2006-2007 respiratory season, 70% of HMPV isolates were genotype A, but a switch to predominantly type B infections occurred next winter. For samples with information on clinical presentations, 26% of HMPV infections were from subjects with lower respiratory tract presentations, lower than recorded for HRSV, but similar to adenovirus, parainfluenza viruses and influenza viruses A and B. Around 13% of HMPV infections were associated with upper respiratory tract symptoms or disease, comparable with other respiratory virus infections. CONCLUSIONS: Numerically and through its association with respiratory disease, HMPV represents a diagnostically significant target that should be included in PCR-based routine screening of respiratory samples. Understanding the biological basis of observed rapid turnover of HMPV variants, including the observed HMPV genotype change between respiratory seasons requires further longitudinal studies.