We investigated the relation between cytomegalovirus (CMV) infection and renal-allograft dysfunction in 14 patients. In seven instances (including two successive transplants in one patient), allograft dysfunction occurred during clinically manifest, viremic CMV infection. In five of these, biopsies revealed little or no tubulointerstitial change but a distinctive, diffuse glomerulopathy characterized by enlargement or necrosis of endothelial cells and accumulation of mononuclear cells and fibrillar material in glomerular capillaries. Two of these allografts recovered their function, both with cessation of high-dose immunosuppression. Biopsies in the other 10 patients revealed predominantly tubulointerstitial changes typical of cellular rejection, and most of these patients did not have viremia. One additional patient, studied prospectively, manifested both forms of allograft injury: tubulointerstitial changes occurring two weeks after transplantation and responding to increased immunosuppression, and CMV-associated glomerulopathy occurring seven weeks after transplantation and responding to decreased immunosuppression. We conclude that viremic CMV infection can cause acute glomerular injury and that recovery may be favored by a decreased in immunosuppressants.