ABSTRACT. In this study we have analyzed various phagocytic functions and tumor necrosis factor (TNF) secretion of human monocytes exposed to either a biochemically well-defined porcine surfactant or a purified phospholipid preparation. Adherence, random migration, and chemotactic response to zymosan activated serum and formyl-methionyl-leucyl-phenylalanine were normal in surfactanttreated monocytes; surfactant was not a chemotactic stimulus. In contrast, phagocytosis of Staphy?vlococcus aureus by monocytes exposed to surfactant (100 pg/mL) or phospholipids (100 pg/mL) was slightly impaired [surfactant:at 30 min (t30) 48.5 f 11%, t o 73.3 + 10.1%; phospholipids: t30 47.3 f 2.5%, Go 68.0 f 6.6%; controls: t30 66.6 + 9.9%, 81.0 f 6.6%, p < 0.05 at t30 for both,p < 0.05 at for phospholipids]. Due to the smaller number of S. aureus ingested, bactericidal activity of surfactant-or phospholipid-treated monocytes was slightly reduced when compared with controls. Surfactant or phospholipids had no bactericidal activity. Uptake of Candida albicans was identical in surfactant-or phospholipid-treated monocytes and untreated controls; the same was true for the number of Candida organisms ingested per cell. Phagocytosisassociated chemiluminescence and production of superoxide anion by monocytes of either source in response to phorbol myristate acetate and opsonized zymosan were also unaffected. Surfactant or phospholipids (500 pg/mL), however, effectively suppressed TNF secretion by resting and by lipopolysaccharide (LPS)-stimulated monocytes in a dose-dependent fashion, (LPS-stimulated monocyte controls: 3004 f 570 pg/mL; LPS + surfactant: 426 + 162 pg/mL; LPS + phospholipids: 28 f 9.6 pg/mL; p < 0.001 for both). TNF is an important mediator of inflammation, and our data suggest that surfactant or phospholipids, by suppressing monocyte TNF secretion, may have an important role in down-regulating inflammatory reactions in the lung. Supported by a grant from Deutsche Forschungsgemeinschaft (Sp 23912-3) (C.P.S.).Surfactant replacement therapy in severe neonatal respiratory distress syndrome effectively reduces respiratory distress syndrome-associated pulmonary morbidity and mortality in preterm infants. Immediately after intrabronchial administration of natural surfactant (human, bovine, porcine), there is a dramatic increase in oxygenation with a subsequent reduction in ventilatory requirements (1). However, there is only limited information about the effect of natural surfactant on human pulmonary monocytes and alveolar macrophages. These cells have an essential role in host defense (2, 3) as well as in the regulation of immune functions and inflammation (4-9). Available data on macrophage-surfactant interaction have been mostly derived from in vitro experiments using lung lavage materials from various species. However, most investigators have focused on a single aspect of macrophage function.Our present study was initiated to examine the principal cell functions of monocytes-the macrophage precursors-in response to inflamma...