A serological survey was used to investigate the epidemiology of cytomegalovirus (CMV) infection in England and Wales. A total of 5237 sera representing the complete age range were used reflecting the general population. The sera were collected in 1991 and 2002, and screened for CMV-specific IgG by ELISA. Antibody prevalence increased with age from approximately 15% in those aged 1-4 years to approximately 80% in those aged > or = 65 years with no association with gender or region. Analysing by common birth cohort demonstrated that between 1991 and 2002 incidence was highest in children born 1985-1989 (1.62% per year, 95% CI 0.86-2.35), lower in older children and younger adults born 1950-1984 (0.75% per year, 95% CI 0.29-1.19) with little evidence of infection in older adults born pre-1950 (0% per year, 95% CI 0-0.64). Application to population and live-birth estimates for England and Wales suggested that between 1991 and 2002, 159 996 (95% CI 67922-278277) CMV infections occurred annually with an annual average of 2133 (95% CI 816-3435) infections affecting pregnant females.