The majority of adults in the world (around 83%) carry antibodies reactive with HCMV and are thought to retain inactive or latent infections lifelong. The virus is transmitted via saliva so infection events are likely to be common. Indeed it is hard to imagine a life without exposure to HCMV. From 45 seronegative individuals (13 renal transplant recipients, 32 healthy adults), we present seven cases who had detectable HCMV DNA in their blood and/or saliva, or a CMV-encoded homologue of IL-10 (vIL-10) in their plasma. One case displayed NK cells characteristic of CMV infection, and HCMV DNA became undetectable. In other cases, the infection may persist with seroconversion blocked by vIL-10. Future research should seek mechanisms that can prevent an individual from seroconverting despite a persistent HCMV infection, as HCMV vaccines may not work well in such people.