The activation of human herpesvirus-6 (HHV-6) commonly coexists with that of cytomegalovirus (CMV) in organ transplant recipients. No data exist of HHV-6 in renal allografts, whereas persistent CMV in the kidney associates with poor outcome and histopathologic changes. We examined HHV-6 and CMV antigens from kidney transplants with previous CMV infection. HHV-6 and CMV pp65 antigens were demonstrated by monoclonal antibodies and immunohistochemistry from 22 kidney transplants with previous CMV infection. CMV was diagnosed by antigenemia tests and/or viral cultures. HHV-6 antigens were found in 7/22 biopsies 18-1330 days after CMV infection, in infiltrating leukocytes in six, and in tubular epithelial cells in two patients. CMV infections were treated, and no virus could be detected from urine or blood thereafter, or at the time of the biopsy. Only 1/7 of these biopsies demonstrated also CMV antigens, whereas CMV antigens were found in 6/15 of the biopsies with no HHV-6. HHV-6 in the graft was associated with previous acute rejections, but not with any histopathological changes or reduced renal function. In conclusion, HHV-6 was a common finding in late renal allograft biopsies of patients with previous CMV infection, but its significance remains to be elucidated.