A 49-year-old woman presented with pulmonary hypertension, profound arterial hypoxemia, and a single-breath carbon monoxide diffusing capacity (DLCO) which was 17% of predicted. History, physical examination, and chest roentgenograms did not suggest the presence of parenchymal pulmonary disease. Spirometry and lung volume measurements were within normal limits. Pulmonary veno-occlusive disease was diagnosed by lung biopsy. This case illustrates the severe reduction of DLCO which can be associated with pulmonary veno-occlusive disease.