We describe the first case of a man who developed acute graft-versus-host disease (GVHD), isolated to the lung, after an orthotopic liver transplant from a female donor. Our patient experienced dyspnea, worsening hypoxemia, and a progressive obstructive ventilatory defect 12 days after liver transplantation. Open-lung biopsy revealed grade 2 lymphocytic bronchiolitis, the pathologic and immunologic correlate of acute pulmonary GVHD. Fluorescent in situ hybridization confirmed donor cells at sites of peribronchiolar inflammation. High-dose corticosteroids were given with a return to baseline pulmonary function. The current case should alert clinicians to investigate pulmonary GVHD as a potential cause of postoperative dyspnea in liver transplant recipient.