Universal screening of congenital cytomegalovirus (CMV) infection without symptoms at birth seems to be necessary to detect late-onset neurodevelopmental sequelae. Congenital CMV infection, as demonstrated by isolation of the virus within the first week of life, was diagnosed in 37 (0.31%) of 11,938 infants born between 1977 and 2002 in the city of Sapporo, Japan, during the 26-year period from January 1977 through December 2002. The characteristics of CMV-specific T-cell immunity was also investigated in pregnant women with primary, latent, or reactivated CMV infection, and in a comparative group of non-pregnant women. The frequency of CMV-specific CD4 T cells in peripheral blood lymphocytes was determined by staining for intracellular cytokines, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α. The frequency of CMV-specific CD4+ T cells in pregnant women associated with CMV reactivation or reinfection was significantly higher than in CMVseropositive normal pregnant and non-pregnant women. The genetic variability of 74 human CMV (HCMV) clinical isolates from 60 Japanese infants and children during 1983 - 2003 was investigated, and the relevance to their clinical course was observed. The hypervariable region of the HCMV genome, that is the a sequence and UL144 region was analyzed using the polymerase chain reaction (PCR) and unrooted phylogenetic trees. HCM glycoprotein B (gB) polymorphism was also investigated. Unrooted phylogenetic trees of a sequence and UL144 allowed the isolates to be grouped to 5 and 3 clades, respectively. Three gB genotypes were also identified. A real-time PCR assay was used to determine vaginal shedding of CMV in 993 healthy pregnant Japanese women and the results were compared with the outcome of pregnancy. HCMV DNA was detected in 76 (7.7%) of the women. The outcome of pregnancy could be determined finally in 848 women, of whom 60 (7.1%) were CMV DNA-positive.  These findings suggest that latent genital tract CMV infection predisposes to adverse pregnancy outcomes.