Pneumocystis carinii pneumonia remains an important, lifethreatening opportunistic infection in immunocompromised patients. It is particularly prevalent among those with AIDS, hematologic or solid malignancies, or transplanted organs and among patients receiving chronic immunosuppressive therapies, particularly corticosteroids (23,25,35,39,59). Histologically, P. carinii pneumonia is characterized by filling of the alveolar space with distinctive protein-rich frothy exudates containing prominent aggregates of organisms (32). The exact chemical nature of the proteinaceous alveolar exudates is not known, but prior studies have shown that these exudates are particularly rich in surfactant proteins A and D (SP-A and SP-D), fibronectin, and vitronectin (54). Interactions of these host components, particularly the surfactant-associated proteins, with P. carinii has been an area of intensive investigation (37,47,53,58,60).Pulmonary surfactant is a complex mixture of lipids and proteins synthesized by alveolar type II cells and secreted into the alveolar spaces. This surfactant exerts multiple functions including reduction of alveolar surface tension and modulation of host defense and inflammatory responses (20,29). It contains at least four associated proteins, of which two, SP-B and SP-C, are hydrophobic and two, SP-A and SP-D, are hydrophilic. SP-A and SP-D have been demonstrated to accumulate during P. carinii pneumonia, while SP-B and SP-C are suppressed during this infection (3,42,44). These surfactantassociated proteins have further been shown to modulate the interaction of P. carinii with host cells and to regulate host inflammatory responses to the organism (26,30,42,57).SP-D is a soluble, collagenous protein synthesized and secreted by type II pneumocytes and nonciliated bronchiolar cells (43). Structurally, it belongs to the group III, mammalian C-type lectin family that includes SP-A, mannose binding protein, and bovine conglutinin (21). SP-D is composed of 43-kDa monomers, each consisting of four major domains: a short cysteine-containing amino-terminal region, a triple helical collagenous domain, a trimeric coiled neck region, and a globular carboxy-terminal carbohydrate recognition domain (CRD) (11). These monomers are assembled into triple helical trimers, which form a single collagenous "arm" displaying the CRDs on the end. Four trimeric subunits undergo disulfide cross-linking within their amino-terminal domains to form a cruciform dodecameric structure (10). Although rat SP-D is assembled as dodecamers, human SP-D appears to consist of a complex of dodecamers and variable proportions of higherorder multimers and trimers (11). In addition, the extent of SP-D binding to P. carinii ligands appears to correlate with the number of CRDs in higher-order multimers of the molecule (55).Recent