Pulmonary alveolar proteinosis (PAP) is a diffuse pulmonary disease of unknown etiology, characterized by the accumulation of large amounts of amorphous phospholipid containing material in the alveolar spaces. Lavaging the lungs with large amounts of saline to remove the accumulated material results in marked clinical improvement and often complete remission. We have examined theperiperal blood and lung lavage material from 6 PAP patients in an attempt to detect abnormalities of the normal immune response. The complete blood counts and the numbers of T and B lymphocytes and monocytes were normal: the lavage fluids contained large numbers of macrophages, most of which were engorged with the amorphous material, and varying numbers of lymphocytes and polymorphonuclear leukocytes. The lavage material inhibited the blastogenic response of mononuclear cells to mitogens: 3HTdR incorporation in response to stimulation with concanavalin-A and Pokeweed mitogen was inhibited in both allogeneic and autologous cells, while response to phytohemagglutinin stimulation was inhibited only in autologous cells. The sera of the PAP patients inhibited 3HTdR incorporation in response to all three mitogens. Neither the lavage material nor the sera inhibited E-rosette formation, nor were they cytotoxic to allogeneic mononuclear cells. Thus while the peripheral blood monoculear cells from patients with PAP appeared to respond normally in vitro, the sera and lavage material contained substances which inhibited the in vitro response of mononuclear cells toi mitogens by interfering with normal monocyte-lymphocyte interactions. The inhibiting material does not appear to be immunoglobulin.