Classic viral pathogenesis models postulate that tissues supporting efficient virus replication promote virus dissemination, which culminates in clinical illness. In this issue of Cell Host & Microbe, Sacher and colleagues use Cre/loxP recombination to label murine cytomegalovirus during replication in distinct cell types in vivo. Strikingly, they demonstrate that the most productive cell type in the host-the hepatocyte-contributes no progeny to dissemination to other tissues.