Cytomegalovirus (CMV) viremia, as measured by a hybrid capture assay, was used to measure the effectiveness of 'immune reconstitution' in human immunodeficiency virus (HIV)-infected subjects treated with highly active antiretroviral therapy (HAART). Of the 28 enrolled patients (mean age, 38 years), 86% were male and 68% were antiretrovirally naive. Of the 23 patients who returned for follow-up, baseline median characteristics were 4.1 log10 CMV DNA copies/106 white blood cells (WBCs), 5.1 log10 HIV RNA copies/mL, and 35 CD4 cells/mm3. After initiation of HAART, median log10 CMV DNA copies/106 WBCs at means of 33, 87, and 385 days were 4.0, 3.3, and 2.5, respectively. Median log10 HIV RNA levels declined from 5.1 to 1.7 at 385 days with a commensurate rise in median CD4 T cells to 166/mm3. Immune reconstitution secondary to HAART results in a significant and progressive decline in CMV viremia in the absence of specific anti-CMV therapy.