A dual role for nitric oxide (NO) in ischemia-reperfusion (I/R) injury is still controversial. This study aims to investigate the role of NO in rat hepatic reperfusion injury. Ischemia was induced by total occlusion of hepatic artery and portal vein for 30 min, then the tissue was reperfused for 30 min. The animals in the L-NAME group (n = 10) received N-G-nitro-L-arginine methyl ester (L-NAME) (15 mg/kg) intraperitoneally 60 min before ischemia. The ischemia group (n = 10) was given an equal volume of saline solution. The control group comprised eight healthy rats which were not exposed to ischemia or reperfusion. An indicator of hepatic injury, plasma alanine amino transferase (ALT) enzyme activities, were increased in the L-NAME group as compared with the ischemia group (p < 0.001). The level of serum nitrite, an index of NO production, and hepatic reduced glutathione (GSH) concentration were lower in the L-NAME group than in the ischemia group (p < 0.001, p < 0.01, respectively). Hepatic levels of malondialdehyde (MDA) and conjugated dienes (CD) were significantly increased in the L-NAME group as compared to the ischemia group (p < 0.05, p < 0.001, respectively). Our results confirm that L-NAME, an inhibitor of the enzyme NO synthase, increased the lipid peroxidation and possibly tissue injury, due to the inhibition of cytoprotective effects of NO in a rat hepatic I/R model. (C) 1999 Published by Elsevier Science B.V. All rights reserved.