Lavage effluents from the lungs of patients with pulmonary alveolar proteinosis were analyzed for soluble constitutents. Antiserums monospecific for normal plasma components, C-reactive protein, and secretory piece were used to investigate the presence of these proteins in lavage effluent, wheras 2-dimensional polyacrylamide gel electrophoresis provided a comprehensive map of the major proteins that were present. The proteins of lung washing obtained from normal subjects and of patient and normal serums were similarly analyzed. Most of the soluble-phase proteins from lavage of patients with pulmonary alveolar proteinosis were also found in patient serum, and were present in amounts consistent with a theory that they originate from the plasma by passage through channels of approximately normal size and selectivity. This findings suggests that the abundant soluble protein found in the alveoli of the lungs of these patients does not arise by leakage through a serverly damaged blood-air barrier. Patients had in their lung lavage effluents 2 soluble proteins of molecular weights 47,000 and 52,000 daltons not found in their serum and not present in lung washings from normal subjects. Uniformly increased concentrations of immunoglobulins in patient lavage effluent, abnormal immunoglobulin concentrations in patient serum, and the presence of C-reactive protein in the serum from 4 of 5 patients indicate a response of the immune system to the disease process and suggest that an atypical hypersensitivity reaction may be involved.