To evaluate the contribution of the respiratory pattern to the ventilatory response after lung transplantation, we studied the changes in minute ventilation, tidal volume, and respiratory rate during CO2 rebreathing in 14 patients with severe obstructive pulmonary disease, and compared them with 10 normal subjects. Seven patients underwent a bilateral lung transplantation and 7 patients had single-lung transplantation. Single-lung transplant recipients increased their respiratory rate by the last postoperative test compared with either preoperative or initial test periods (0.38 ± 0.13 versus 0.027 ± 0.24 or 0.12 ± 0.08 breaths · min-1 · mm Hg-1; P < 0.005). Bilateral lung transplant recipients showed a diminished ability to augment their respiratory rate by the last postoperative test compared with either preoperative or initial test periods (0.13 ± 0.23 versus 0.54 ± 0.25 or 0.25 ± 0.29 breaths · min-1 · mm Hg-1; p < 0.06). The restored ventilatory response by the fourth postoperative week was due to a statistically significant increase in tidal volume for both single and bilateral lung transplant recipients. This study demonstrates that when lung transplant recipients have an appropriate ventilatory response to CO2 rebreathing, single-lung transplant recipients have a respiratory pattern similar to normal; whereas the bilateral lung transplant recipients show the effects of total pulmonary denervation. We conclude that the preserved ventilatory response in lung transplant recipients is composed of a respiratory pattern that is influenced by the presence or absence of vagal inputs.