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Manifest polyomavirus (PV) renal graft infection is a rare complication. We diagnosed 5 cases among 70 kidney recipients undergoing transplants since December 1995; however, there were no cases at our institution before December 1995.To identify risk factors promoting manifest PV graft infection, we compared those 5 patients with kidney recipients who had signs of PV replication but no manifest graft infection (n=23, control group). PV replication was judged by the presence of intranuclear inclusion cells in the urine.Before the infection, five of five patients had recurrent rejection episodes. All were switched from cyclosporine A to high dose tacrolimus as rescue therapy. Infection was diagnosed histologically 9±2 months posttransplantation; it persisted and led to graft loss in four of five patients. In control patients, graft function was stable, 1 of 23 patients were switched to tacrolimus as rescue therapy, and graft loss occurred in 4 of 23 patients.Recurrent rejection episodes and high dose immunosuppressive therapy, including tacrolimus, are risk factors for manifest PV kidney graft infection, which has an ominous prognosis.