This study evaluates the utility of quantitative polymerase chain reaction (QPCR) to determine duration of treatment of transplant patients with human cytomegalovirus (HCMV) disease. Eighteen patients with HCMV disease were prospectively evaluated and followed for recurrence using a QPCR assay. We used plasma samples from which nucleic acid was extracted. Quantification was determined by using an internal standard that contained the same primer sequences as for HCMV. During treatment, weekly QPCR assays were performed. Patients were treated with HCMV immunoglobulin-G for a finite period, but intravenous ganciclovir was continued until less than 100 viral copies (vc) per mL was detectable. After cessation of therapy, patients were followed for 6 months with monthly clinical assessment and QPCR. No patient developed recurrence of HCMV at a mean follow-up of 16 months. This preliminary study suggests that the use of QPCR to assess viral load is useful in deciding the length of HCMV treatment with ganciclovir but requires further randomized validation.