Herpesviruses have been implicated as potential initiators of a variety of endothelial pathologies [1] [2] [3] [4] . Given the intimate interactions observed between herpesviruses and endothelial cells, and the systemic spread of cHV68 during infection, we characterized the outcome of endothelial cell infection with cHV68, a small animal model for the human gammaherpesviruses. While cHV68 replicated comparably in endothelial cells and fibroblasts up to 36 hours post-infection, infected cultures of endothelial cells had a high percentage of viable, non-adherent cells that remained following infection. Of significance, these viable, non-adherent cells had not simply escaped infection, but instead were actively infected, as determined by the presence of multiple markers of the lytic replication program. While the absolute number of viable, infected endothelial cells varied among different cell lines and primary cells, the prolonged viability of endothelial cells in comparison to fibroblasts was remarkably consistent in endothelial cell lines from distinct anatomic locations, as well as in primary endothelial cells. Furthermore, optimal survival of both endothelial cell lines and primary endothelial cells was dependent on the presence of the cHV68 v-cyclin, indicating that this outcome was a process actively promoted by virus infection.