BACKGROUND: Nitric oxide (NO) may act as an oxygen radical scavenger or as an antioxidant, and inhibit neutrophil superoxide anion production. In contrast, NO combines with superoxide to form peroxynitrite, a very damaging material whose decomposition RESULTS in the generation of a hydroxyl radical. This study was designed to determine the role of NO in the development of acute lung injury and lipid peroxidation induced by lipopolysaccharide (LPS) in rats. METHODS: Male Sprague-Dawley rats (200 - 250 g) were given one of the following treatments; intraperitoneal normal saline 0.5 ml, intraperitoneal E. coli LPS (5 mg/kg) in 0.5 ml normal saline, 4 mg/kg L-N(6)-(1-iminoethyl)lysine (L-NIL) + LPS, or L-arginine (80 mg/kg) + LPS. Four hours after treatment, the rats were killed by an intraperitoneal pentobarbital injection (100 mg/kg) and plasma nitrate/nitrite concentration (Griess reagents) and lipid peroxide (LPO) concentration of the lung (Yagi's method) were measured (n = 8). In the other sets of experiments, myeloperoxidase activity of the lung (n = 5) and protein concentration of the bronchoalveolar lavage (BAL) fluid (BCA protein assay reagents, n = 4) were assayed. RESULTS: LPS treatment increased plasma nitrate/nitrite concentrations approximately 6 times (20.9 1.8nM, P < 0.01) compared with the control group (3.6 +/- 0.7nM), and L-NIL treatment prevented this increase. L-NIL plus LPS treatment resulted in greater increase of LPO concentrations of the lung compared with the control (P < 0.05). Myeloperoxidase activity and protein concentrations of BAL fluids were higher in LPS and L-NIL plus LPS treatment groups than the control group. CONCLUSIONS: These results suggest that inhibition of the increase of NO by selective inducible NO synthase inhibitor L-NIL may increase lipid peroxidation in septic rats.