In Type B Niemann-Pick disease, progressive pulmonary infiltration is a major cause of morbidity and mortality, although the disease is usually diagnosed before adulthood in other organ systems. To date, no successful treatment of pulmonary involvement by Niemann-Pick disease has been documented. We describe the case of a patient with Niemann-Pick Type B disease who presented with extensive endogenous lipoid pneumonia and life-threatening hypoxia following bypass grafting for severe coronary artery disease. A surgical lung biopsy at the time of grafting revealed characteristic histology and ultrastructural features of Niemann-Pick disease, with confirmatory findings in biochemical studies. Because of the severity of the patient's symptoms, bilateral whole-lung lavage was undertaken, leading to symptomatic improvement, lessening of parenchymal opacification on high-resolution computed tomographic scanning, and a marked improvement in resting arterial oxygen tension while breathing air to 10.3 kPa from 8.4 kPa. Whole-lung lavage may be a potentially useful modality of treatment for patients with pulmonary involvement by Niemann-Pick Type B disease.