Pulmonary alveolar proteinosis is a disorder of surfactant deposition that leads to the accumulation of lipoproteinaceous material in the alveoli. The mainstay of treatment is whole-lung lavage, by which saline is used to wash the alveolar deposits from the lung. Patients are currently followed using sequential preand post-lavage CT to subjectively assess treatment efficacy. We present an approach to quantify global and regional changes in disease distribution before and after lavage using automated and semiautomated segmentation methods. Histogram analysis demonstrates a leftward shift in parenchymal intensities after lavage, reflecting an increase in the degree of aerated lung after removal of excess surfactant. This methodology can be applied to a variety of pulmonary pathologies that manifest as a combination of alveolar and interstitial disease, to enable more quantitative assessment of disease progression and treatment efficacy.