Clinical disorders with an isolated lack of monocytes have not been reported hitherto. The authors describe the case of a 38-year-old woman with pulmonary alveolar proteinosis and nephrotic syndrome caused by membranous nephropathy and widespread papillomatosis of the vulva. Immunologic studies showed normal levels of immunoglobulins and C2, C3c, and C4. Cryoglobulins and paraproteins were not detected. Antinuclear antibodies, antineutrophil cytoplasmic antibodies, and antiglomerular basement membrane antibodies were not detectable. Circulating immune complexes containing C1q, immunoglobulin G, and immunoglobulin M were elevated. The patient showed immunodeficiency that was characterized by complete anergy to intracutaneously administered recall antigens in vivo and to recall antigens in vitro. The immunodeficiency was accompanied by the absence of monocytes in the peripheral blood as well as in bone marrow cultures. In parallel, long-term bone marrow cultures and colony-forming cell assays did not result in the growth of monocytes. Mitogenic agents that require the presence of monocytes induced almost no T-cell proliferation (Concanavalin A: 5,841 counts per minute [cpm]), whereas agents that act directly on T cells induced intense T-cell proliferation (phytohemagglutinin: 110,001 cpm; OKT 3: 120,616 cpm; and pokeweed mitogen: 89,474 cpm). These data suggest that the pulmonary renal syndrome in this patient results from the lack of monocytes and the consecutive defect of antigen presentation and antigen clearance.