In combined heart-lung transplantation the afferent nerve pathways inevitably are transsected. In previous studies with en bloc heart-lung transplantation in dogs, we found altered regulation of breathing-abolition of Hering-Breuer reflex and response to hypercapnia inhalation stimulus consisting of augmented tidal volume with no change in respiratory rate-shortly after the operation. The long-term effects of pulmonary denervation on breathing regulation were now studied in dogs after staged bilateral pulmonary autotransplantation. Mechanical and electrical activities of the respiratory muscles were recorded during spontaneous breathing and after deflation and inflation with varying volumes of air. Five months postoperatively the duration of the respiratory cycle increased 2.5 times on inflation with 600 ml of air and occlusion of the airways, compared with tenfold prolongation in intact control dogs, indicating a partial return of the Hering-Breuer reflex after the autotransplantation. The duration of the EMG bursts in respiratory muscles increased in intact dogs and in those with bilateral lung autotransplants. In impulse frequency the response to stretching was less evident after autotransplantation. The mechanism mediating reappearance of Hering-Breuer reflex warrants further study.