The ratio of human cytomegalovirus (HCMV) genomes per cellular genomes in serial peripheral blood leukocyte (PBL) extracts of renal allograft recipients was quantitated by competitive nested polymerase chain reaction (PCR). Patients were also monitored for the development of acute HCMV infection by detection of HCMV pp65 antigenemia, HCMV IgM antibodies, and viruria. Compared to qualitative nested HCMV PCR, the frequency of positive PCR results in renal allograft recipients without further evidence of acute HCMV infection was significantly reduced by quantitative HCMV PCR. HCMV DNA levels > or = 1,000 copies HCMV/10(6) copies beta-globin were found to be highly indicative for the development of a clinically symptomatic HCMV infection following renal allograft transplantation. In patients treated with ganciclovir, quantitation of HCMV target sequences allowed the assessment of the efficacy of antiviral therapy.