We have provided evidence for cHV68 infection of endothelial cells in vivo at early times post-infection. Interestingly, infected cells (including endothelial cells) were not abundant in acutely infected lung tissue, as little to no GFP was detected by flow cytometric analysis of unfractionated lung cells after infection with a GFPmarked virus (data not shown), but required sensitive PCR methods for detection. Our in vitro analysis demonstrated a change in surface phenotype of infected endothelial cells which could correspond to substrate detachment and release into circulation. This is an intriguing idea in light of published reports of circulating endothelial cells and progenitor endothelial cells in virus infection. Our in vitro studies implicated endothelial cells as a persistent source of virus production, however, the extent to which endothelial cells contribute to cHV68 persistence in vivo, and to what degree it might be influenced by host immune status, are important issues that remains to be addressed. While it is unlikely that an intact immune response would permit such long-term expression of viral antigens in vivo, we hypothesize that persistently infected endothelial cells could provide a significant source of continued virus replication in immune-compromised individuals (i.e. AIDS patients), a context in which gammaherpesvirusassociated pathology frequently occurs.