During a three year period in which 433 renal transplants were performed, 194 episodes of fever were documented in allograft recipients hospitalized at the University of Minnesota. Viral infections were responsible for over half of the febrile episodes, and 98 (51 percent) of the fevers were associated with cytomegalovirus (CMV), either occurring alone or in conjunction with allograft rejection or another systemic infection. Bacterial infections, fungal infections and rejection were other important causes of fever, accounting for 14 percent, 5 percent and 13 percent of the febrile episodes, respectively. Most fevers occurred in the first four months after transplantation; although about two thirds of these fevers were due to CMV, only 17 percent of fevers that occurred more than one year after the renal transplant were due to CMV. Bacterial and fungal infections and malignancy were important causes of these fevers. Of the febrile illnesses associated with transplant nephrectomy or death, a majority occurred in patients with CMV disease. Secondary bacterial and/or fungal infections were observed in a large majority of patients with lethal CMV disease. During the third year of this study there was a significant decrease in the proportion of febrile episodes due to CMV.