We have previously shown that lung surfactant and Survanta(a surfactant substitute) inhibit NO production induced by LPS in rat alveolar macrophages (Miles et al., Am.J.Physiol., in press). We studied the effect of Survanta (200 microg phospholipid/ml) on NO production in two monocytic cell lines, J-774A.l and Raw-264.7, and found that it does not inhibit NO production induced by LPS (1 microg/ml) plus interferon-y (25 U/ml). The effect on NO was characterized by measuring NO production by the Griess reaction, NO message by a ribonuclease protection assay and NO protein synthesis by Western blotting. Survanta had no effect on any of the parameters. In contrast, interleukin-13 (IL-I3), a cytokine known to inhibit NO production by decreasing NO message and protein synthesis, had the expected effect in these two cell lines. The observations indicate that the effect of lung surfactant on NO production is cell-specific. In alveolar macrophages, lung surfactant decreases NO production by decreasing NO protein levels without decreasing NO message levels, indicating that the regulation may be occurring at the transitional level. The differential effects of Survanta on rat alveolar macrophages and these monocytic cell lines may offer a useful model for delineating the molecular mechanisms, regulating NO production in inflammatory cells.