Objective. We assessed a new cytomegalovirus (CMV) DNA hybridization assay, We also compared the assay with other currently used assays to determine its use in the early detection of active CMV infection. Patients and Methods. Sequential whole blood samples collected from 109 patients who had undergone orthotopic liver transplantation were tested using the Murex hybrid capture system, cell culture, antigen detection, and serology. Liver biopsies performed during the study period for graft dysfunction in 84 patients were examined for histological features of CMV hepatitis, The biopsies were also immunostained for the presence of CMV antigens. Results. Fifteen patients developed clinically significant CMV disease (CMV syndrome in six patients and CMV hepatitis in nine patients, including two patients with disseminated CMV disease), In all 15, CMV DNA was detected by the hybrid capture assay between 1 and 20 days before other CMV assays, Fourteen of the 15 patients had CMV DNA levels greater than 50 pg/ml; the other patient had a value of 48 pg/ml. Of the remaining 94 patients with no evidence of CMV disease, 86 were negative by the hybrid capture assay and 8 were positive; all but one patient had values less than 50 pg/ml, DNA levels fell rapidly in all patients during antiviral therapy. Conclusion. Unlike conventional CMV detection methods, this hybridization assay is an early predictor of clinically significant CMV infection after liver transplantation and also provides quantitation of viral load, allowing monitoring of antiviral therapy.