We report the case of a 45-year-old burned man (55% total body surface area full-thickness burn) who developed symptomatic cytomegalovirus infection during cyclosporine (CSA) therapy (3 mg/kg orally) for skin transplantation. During the sixth hospital week the patient developed signs compatible with CMV infection, and CMV was recovered from the urine and sputum. Examination of skin biopsy specimens from the transplanted cadaver allograft revealed inclusion bodies compatible with CMV infection, and CMV antigens were detected by immunohistochemical testing. The CMV infection of the skin was confirmed by recovery of infectious virus and by detection of CMV nucleic acids using in situ hybridization with a biotinylated HCMV DNA probe. Restriction enzyme analysis of a urine CMV isolate and two isolates from skin demonstrated differences in DNA patterns, suggesting that the patient was infected simultaneously with two different CMV strains.