The first-line treatment for PTLD is reduction in immunosuppression, allowing partial reconstitution of cell-mediated immunity. However, there is a risk of inducing acute allograft rejection during clinical resolution of PTLD. A recently available assay, Immuknow, measures the cell-mediated immune response and could be used to monitor reduction of immunosuppression. We report a case of PTLD occurring in a pediatric kidney transplant recipient where the reduction in immunosuppression was serially followed using this assay and quantitative EBV-PCR. A rapid reduction to minimal immunosuppression was followed by resolution of PTLD. Later, when the cell-mediated immune response increased, with negative viral load, immunosuppression was gradually increased utilizing the assay to adjust dosing. Presently, there are no signs of PTLD and renal function remains normal.