This study was designed to clarify the effects of pentoxifylline (PTX) and N-acetylcysteine (NAC) on hepatic reperfusion injury in rats. Rats were pretreated with NAG, or PTX, or combination of the drugs. In each rat, liver was isolated after twenty minutes reperfusion following thirty minutes ischemia. Plasma alanine amino transferase (ALT) activity, liver tissue glutathione (GSH) and malondialdehyde (MDA) levels, glutathione peroxidase (GPx), glutathione reductase (GSSGR), superoxide dismutase (SOD) and catalase (CAT) activities were determined. Plasma ALT activity was higher in ischemia/reperfusion groups than in control. It was decreased in the groups given NAG. Administration of NAC maintained tissue GSH levels, whereas the levels were decreased in both the ischemia/reperfusion groups treated (P < 0.05) and untreated with PTX (P < 0.01). Increases in liver MDA concentration in ischemia/reperfusion (P < 0.01) and PTX-treated groups (P < 0.05) were mitigated by administration of NAG. GPx and CAT activities were increased in the ischemia/reperfusion (P < 0.01, P < 0.05) and PTX-treated groups (P < 0.05, P < 0.001). GSSGR activities were increased in the NAC (P < 0.001) and NAC-PTX-treated groups (P < 0.01). SOD activities were higher in the ischemia/reperfusion (P < 0.01) and the PTX-treated (P < 0.01) and the NAC-PTX-treated groups (P < 0.01). In conclusion, short-term liver ischemia/reperfusion diminished GSH, increased MDA and induced some antioxidant enzymes. While we could not find any useful effects with PTX as we expected, our findings indicate that NAC might be useful to prevent tissue damage in hepatic ischemia/reperfusion injury. (C) 1998 Elsevier Science B.V. All rights reserved.