Formalin fixed paraffin-embedded lung tissues (n = 13) or lavage material (n = 4) from 17 patients in whom alveolar proteinosis was the primary disease and ten patients with other primary diagnoses but lung morphology similar to alveolar proteinosis were examined. The tissues were stained by the periodic acid-Schiff method and by the immunoperoxidase method for surfactant specific apoprotein. The intra-alveolar material in patients with primary alveolar proteinosis stained uniformly for surfactant specific apoprotein, whereas the staining was focal in patients with other primary diseases associated with intra-alveolar accumulation of proteinacious material. In both situations, the number of inflammatory cells, especially macrophages, was small. These observations extend an earlier impression about the presence of surfactant specific apoprotein in alveolar spaces in patients with primary alveolar proteinosis and provide a distinction between primary alveolar proteinosis and morphologically similar appearance due to other causes, ie, secondary alveolar proteinosis. The lack of macrophages in the affected tissue appears to be the major pathogenetic factor in alveolar proteinosis.