Kidneys from twelve renal transplant recipients were examined prior to and after graft failure and explantation. The investigations included conventional light and electron microscopy and the analysis of human cytomegalovirus-related viral proteins and viral DNA. Nucleic acid hybridization studies were conducted on kidney explants by an in situ method using DNA probes and by the polymerase chain reaction employing primers and probe for immediate early gene targets. In none of the cases did light and electron microscopy including immunohistochemistry for human cytomegalovirus reveal active infection in punch biopsies or explants. Interestingly, in situ hybridization also failed to detect human cytomegalovirus even in two cases with seroconversion, while the polymerase chain reaction was positive. The polymerase chain reaction disclosed only two additional positive cases within the residual group of explanted kidneys. In our hands, the polymerase chain reaction was the only potent direct detection method for cytomegalovirus in transplanted human kidneys.