Urine and blood leukocyte cultures and qualitative plasma polymerase chain reaction (PCR) and quantitative competitive (QC) PCR were evaluated for their ability to identify AIDS patients at risk for human cytomegalovirus (HCMV) disease. AIDS patients were followed with urine and blood specimens every 3 months. During a mean follow-up of 12 months, 26 (28%) developed HCMV disease. The sensitivity, specificity, positive predictive value, and negative predictive value for urine culture were 85%, 29%, 31%, and 83%; for leukocyte culture were 38%, 74%, 69%, and 81%; for qualitative plasma PCR were 89%, 75%, 58%, and 94%; for QC-PCR (> 1000 copies/μL) were 35%, 100%, 100%, and 80%; and for QC-PCR (>100 copies/μL) were 73%, 90%, 73%, and 90%, respectively. Of 41 patients identified by qualitative PCR to have HCMV DNA in plasma, the 24 who developed HCMV disease had 1510 ± 448 (mean ± SE) peak copies of HCMV DNA/μL by QC-PCR, versus 161 ± 52 for the 17 patients who did not develop disease (P = .0007). Thus, plasma PCR is superior to culture for identification of AIDS patients at risk for HCMV disease, and quantitation of plasma DNA further identifies high-risk persons.