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 surfactant-treated monocytes; surfactant was not a chemotactic stimulus. In contrast, phagocytosis of Staphylococcus aureus by monocytes exposed to surfactant (100 μg/mL) or phospholipids (100 μg/mL) was slightly impaired [surfactant: at 30 min (t30) 48.5 ± 11%, t60 73.3 ± 10.1%; phospholipids: t30 47.3 ± 2.5%, t60 68.0 ± 6.6%; controls: t30 66.6 ± 9.9%, t60 81.0 ± 6.6%, p < 0.05 at t30 for both, p < 0.05 at t60 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. Phagocytosis-associated 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 μg/mL), however, effectively suppressed TNF secretion by resting and by lipopolysaccharide (LPS)-stimulated monocytes in a dose-dependent fashion, (LPS-stimulated monocyte controls: 3004 ± 570 pg/mL; LPS + surfactant: 426 ± 162 pg/mL; LPS + phospholipids: 28 ± 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.