To assess airway reactivity in lung transplant patients, three heart/lung, three double lung, and eight single lung transplant patients underwent airway challenge tests. All patients were assessed by methacholine aerosol challenge and thirteen were also assessed by histamine aerosol challenge at least three months after transplant surgery. The airways of patients with bilaterally denervated lungs (heart/lung and double lung transplants) were significantly more reactive to both methacholine and histamine (p less than 0.01) than were the airways of patients with unilaterally denervated (single lung transplants) lungs. Inflammatory changes in the airway mucosal biopsies were minimal in three patients and absent in all others. These studies raise questions about the role of central innervation in the maintenance of normal airway function as well as the mechanisms of action of both methacholine and histamine in causing bronchoconstriction.