In order to examine the role of Epstein-Barr virus (EBV) in the pathogenesis of chronic active EBV infection (CAEBV), we investigated whether or not EBV integration into the human genome is associated with any chromosonal abnormality. We therefore analyzed 4 cases of CAEBV: 2 cases showed a normal karyotype, while one had an oligo-clonal 6th chromosomal abnormality and the fourth had a clonal 6th deletion (q15q23). In addition, the case with an oligo-clonal abnormality also had oligo-clonal EBV terminal repeat (TR) bands, while the case with a clonal abnormality showed a clonal TR band. In contrast, the 2 cases with a normal karyotype showed no clonal band. Two-color fluorescence in situ hybridization (FISH) was used to detect the integrated EBV and the 6th chromosomal site. The presence of integrated EBV into the 6th chromosome was not frequent in the 2 cases with a normal karyotype, but it was statistically frequent in the case with an oligo-clonal 6th abnormality. In the case with a clonal 6th deletion, integration in the 6th chromosome was also slightly higher than that in the other chromosomes. In CAEBV, integrated EBV might thus be associated both with chromosomal abnormality and with pathogenesis.