We examined the effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on human cytomegalovirus (CMV) replication in the human embryonic fibroblast cell line, MRC-5. Treatment of cells with 0.0001 pg/ml TCDD augmented the cytopathic effects of CMV-infected MRC-5 cells. Moreover, TCDD increased the replication of intracellular CMV without affecting the proliferation of host cells, with a concomitant increase in CMV UL54 DNA levels. However, TCDD demonstrated no virocidal effect on cell-free CMV. Furthermore, CMV-infected MRC-5 cells expressed transcripts of the aryl hydrocarbon receptor (AhR) and AhR nuclear translocator. These results suggest that TCDD may contribute to the development of opportunistic diseases by reactivation of latently infected CMV and that TCDD regulates CMV replication through the dependence on AhR. (C) 2002 Elsevier Science (USA). All rights reserved.