Diagnosis of polyomavirus BK nephropathy and treatment by low-dose immunosuppression may be optimized by using surrogate markers, such as the detection of viral inclusion bearing cells in the urine and polyomavirus BK DNA in plasma by polymerase chain reaction. These markers were used prospectively in the management of a 44-year-old woman and led to the diagnosis of polyomavirus BK nephropathy at an early stage. The management was complicated by the concurrence of acute allograft rejection. Two treatment steps were initiated: antirejection therapy consisting of methylprednisolone for 3 days followed by lowering of the maintenance immunosuppression. This treatment resulted in a return of the serum creatinine concentration to the baseline of 1.6 mg/L, clearance of polyomavirus BK from plasma, and disappearance of viral inclusion bearing cells from the urine. After 2 months of stable allograft function, a control biopsy confirmed the resolution of polyomavirus BK nephropathy. Histologic signs of acute interstitial rejection were found and preemptively treated by methylprednisolone without altering the baseline regimen. Allograft function remained stable without evidence of recurrent polyomavirus BK nephropathy. This case shows the value of surrogate markers used in a prospective fashion for diagnosis and management of polyomavirus BK nephropathy with concurrent rejection.