Experiments were designed to compare the function of the endothelium and smooth muscle in intralobar pulmonary arteries and veins of transplanted lungs during acute rejection and after treatment of rejection. Single lung allografts were performed in dogs. Dogs were monitored for 5 days to allow good recovery from the operation and resolution of early chest radiographic changes. In group I, immunosuppression (cyclosporine A, azathioprine, and methylprednisone) was withdrawn to allow rejection, which typically occurred after 3 days. In group II, immunosuppression was reinstituted at this time during acute rejection until the chest roentgenograms again cleared (approximately after 6 days). The blood vessels were studied at this time. Rings were cut from intralobar pulmonary arteries and veins of the allotransplanted lungs and suspended for the measurement of isometric force in organ chambers. Contractions of arteries and veins to phenylephrine but not endothelin-1 were significantly reduced during acute rejection. In arteries and veins, endothelium-dependent relaxations to bradykinin but not the calcium ionophore A23187 were reduced with rejection. Relaxations of the smooth muscle to histamine increased with rejection in both blood vessels. Relaxations to nitric oxide were reduced with rejection in veins but not arteries. Treatment of rejection reversed all responses toward those observed in arteries and veins in lungs from dogs not undergoing transplantation. These results suggest that responses of the endothelium and smooth muscle of pulmonary arteries and veins of transplanted lungs are altered similarly during rejection. Further, treatment of rejection restores function of the pulmonary blood vessels of lung allografts toward that observed in unoperated lungs.