Cardiopulmonary limitations to exercise in restrictive lung disease. Med. Sci. Sports Exerc., Vol. 31, No. 1 (Suppl.), pp. S28-S32, 1999. Restrictive lung disease encompasses a large and diverse group of disorders characterized by a diminished lung volume. These disorders exhibit common pathophysiologic features including abnormal gas exchange caused by loss of functioning alveolar-capillary unit, abnormal respiratory muscle energetics caused by altered mechanical ventilatory function, and secondary hemodynamic and cardiac dysfunction. Impaired gas exchange is the most prominent exercise abnormality in interstitial lung disease and eventually develops in other causes of lung restriction as well. Measurements of diffusing capacity (DLCO) and alveolar-arterial oxygen tension gradient during exercise are more sensitive detectors of disease than measurements at rest. Excessive dead space ventilation is common in pulmonary parenchymal, pleural, and thoracic diseases, leading to a higher minute ventilation and ventilatory work during exercise. The associated increase in the metabolic energy requirement of respiratory muscles may exceed 50% of available total body oxygen delivery and result in insufficient energy delivery to nonrespiratory muscles that sustain locomotion. Pulmonary arterial hypertension develops secondarily to an increased pulmonary vascular resistance. In addition, diastolic filling of the ventricles during exercise may be restricted by pulmonary fibrosis or anatomical restriction of the pleura and thorax, contributing to secondary cardiac dysfunction. Examples of heart-lung interaction are illustrated by the patient after unilateral pneumonectomy. These pathophysiologic changes help explain why functional disability in these patients is often out proportion to the impairment in lung function.