Pulmonary alveolar proteinosis (PAP) is defined by abnormal accumulation of surfactant that fills the alveolar spaces; this material is coarsely granular and strongly positive with digested PAS stain. Ninety percent of PAP cases are autoimmune and caused by high levels of anti-granulocyte-macrophage-colony stimulating factor (GM-CSF) antibodies; these antibodies prevent alveolar macrophages from taking up and degrading surfactant. Other causes of PAP include malignancies, especially hematologic malignancies, exposure to high levels of finely divided dusts, drugs, and, in a small number of cases, mutations in surfactant or GM-CSF or GM-CSF receptor genes. Treatment is whole lung lavage and/or inhaled GM-CSF.