Many humans harbor clinically quiescent or latent CMV. Even when asymptomatic, the virus may cause indirect effects, possibly by altering immune system function after subclinical reactivation episodes or by expression of viral genes (e.g., LAcmvIl-10) during latency. Immune system dysfunction resulting from a variety of iatrogenic or natural causes or from a new transmission event can lead to active CMV replication. Depending on the clinical setting, active replication may contribute to indirect effects, but also leads to direct tissue damage, resulting in an inflammatory response and dysfunction of various organ systems. In addition to CMV antigenemia, a common indicator of active infection, examples of end CMV organ disease commonly occurring in AIDS patients and in transplant recipients are shown. Image credits: antigenemia, pp65⁺ cell in a leukocyte cytospin preparation (M. Boeckh); retinitis, ophthalmoscopic view of retinal hemorrhage and inflammation (E. Chuang); ependymitis, periventricular inflammation detected by MRI (left; reproduced from ref. 119 with permission from McGraw Hill) and postmortem brain specimen (right; C. Marra); hepatitis, microabscesses associated with CMV hepatitis (A. Limaye); esophagitis, endoscopic view of shallow esophageal ulcers (G. McDonald); colitis, deep ulcer in a colonic biopsy (G. McDonald); pneumonia, chest CT scan of CMV pneumonia (M. Boeckh).