A 37-yr-old man with pulmonary alveolar microlithiasis (PAM) presented with respiratory failure and cor pulmonale. The FEV1/FVC was 1.4/1.8 L with total lung capacity of 3.2 L using the helium dilution method (54% predicted) and 6.1 L using body plethysmography (102% predicted), indicating large noncommunicating regions. The KCO (transfer factor per liter lung volume) was 3.05 ml/min/mm Hg/L (47% predicted). Despite home oxygen (3 L/min) and diuretic therapy, the patient remained hypoxic (PaO2, 55 mm Hg) and incapacitated with dyspnea. Nasal continuous positive airway pressure (nCPAP) at 12 cm H2O and oxygen at 1 L/min improved his oxygenation (PaO2, 93 mm Hg), and introduction of this regimen at night resulted in subjective improvement in daytime function. A Grandjean right heart catheter was introduced at the bedside, and the multiple inert gas elimination technique (MIGET) was used to measure ventilation and blood flow distributions at ambient pressure and with the addition of 10 cm H2O nCPAP. The patient had severe pulmonary hypertension (mean Ppa, 57 mm Hg) and severe hypoxemia (PaO2 37 mm Hg), which was mainly due to shunt (16% of cardiac output) and a broadening of the main mode of the ventilation-perfusion (VA/Q) distribution (log SD Q, 0.94). There was a significant reduction in shunt during nCPAP to 6% of cardiac output without increasing Ppa, and this effect appeared to extend past the period of application. We conclude that nCPAP reduces intrapulmonary shunt in this rare condition and allows for correction of hypoxemia with a smaller oxygen flow rate.