A 14-year-old boy with end-stage renal failure secondary to reflux nephropathy received a renal transplant and was immunosuppressed with prednisone, azathioprine, and Minnesota antilymphoblast globulin, followed by cyclosporine A. A renal biopsy was performed 43 days post-transplantation because of fever and an elevated serum creatinine. The biopsy showed a mild interstitial lymphocytic infiltrate and immunosuppression was not changed. A second renal biopsy was performed 66 days after transplantation because of a persistent elevation of the serum creatinine following a cytomegalovirus (CMV) infection. CMV inclusions were seen by light microscopy (LM) in glomerular and peritubular capillary endothelial cells and tubular epithelial cells but no viral inclusions were present on the grids examined by electron microscopy (EM). However, the inclusions seen by LM were confirmed as CMV by immunohistochemistry, using polyclonal and monoclonal antibodies to CMV, and by in situ hybridization, using a biotinylated CMV DNA probe, emphasizing the usefulness of these techniques when studies by EM are not contributory.