Background. Increased nitric oxide production accompanies acute lung allograft rejection. Transforming growth factor-β1 is an immunosuppressive cytokine capable of ameliorating acute rejection. The purpose of this study was to determine whether exhaled nitric oxide (eNO) concentrations correlated with the degree of acute rejection. Methods. A model of acute lung transplant rejection in the rat was developed, and concentrations of eNO were measured at the time of animal sacrifice. In group 1 (partial immunosuppression), donor lungs were pretreated with transforming growth factor-β1 before implantation. In group 2 (fulminant acute rejection), no immunosuppression was used. In group 3 (full immunosuppression), recipients received cyclosporine. Group 4 were normal rats. Results. When measured from both lungs, eNO concentrations were 4.97 ± 0.68 versus 6.73 ± 2.90 ppb for groups 1 and 2, respectively (p = 0.58). When measured selectively from transplanted left lungs, eNO concentrations were 8.61 ± 0.97 versus 42.14 ± 7.27 ppb, respectively (p < 0.001). In groups 3 and 4, eNO concentrations were 1.02 ± 0.21 and 1.51 ± 0.74 ppb, respectively. Conclusions. Exhaled nitric oxide is elevated in fulminant acute rejection, is reduced after partial immunosuppression using transforming growth factor-β1 gene therapy, and is in the normal range in cyclosporine-treated animals. The measurement of eNO correlates with the degree of acute lung allograft rejection and may serve as a noninvasive measure of acute lung transplant rejection in the clinical setting. (C) 2000 by The Society of Thoracic Surgeons.