Dyspnea with exertion is nearly always present in patients with pulmonary lymphangioleiomyomatosis, but the mechanisms underlying exercise impairment have not been well defined. Spirometry, lung volumes, lung mechanics, and exercise physiology were performed on a cohort of 16 patients. We determined the relative contribution of airflow limitation, gas exchange abnormalities, and pulmonary vascular abnormalities to the exercise performance achieved. The patients had normal TLC and Vtg, but RV was elevated in 88% of the subjects. A moderate to severe obstructive pattern was present in 69% of the subjects, and the DLCO was reduced, often markedly, in 81% of the subjects. Exercise performance was limited (work load, 68% +/- 6) with abnormalities of ventilatory function and gas exchange present. Strong correlations between overall exercise performance (percent predicted VO2max and maximal work load achieved) and indices of airflow and vascular involvement were present. Poor exercise performance was due primarily to ventilatory limitation. The etiology of this ventilatory limitation appears twofold. First, subjects had a reduced ventilatory ceiling because of airflow limitation. Second, subjects demonstrated an excessive ventilatory response as a result of increased dead-space ventilation thought to be due to disease-associated cystic changes and associated pulmonary vascular dysfunction or destruction.