The administration of glutamine before experimental ischemia/reperfusion (I/R) has been shown to protect intestinal, pulmonary, and myocardial tissue by inducing heat shock proteins (HSP). However, it is not known whether glutamine is protective for all organs. We therefore tested whether pretreatment with glutamine reduces injury following hepatic I/R in rats. Male lean Zucker rats were pretreated with either glutamine (0.75 g/kg intraperitoneally, n = 6) or saline (n = 6), 24 and 6 hours before ischemia. Seventy percent of the liver was exposed to 75 minutes of warm ischemia followed by 24 hours reperfusion. Liver enzymes, histology, neutrophil accumulation, survival, and heat shock protein (HSP) 70 induction were examined. Glutamine administration did not reduce liver injury. In both groups, 5 of 6 animals survived 24 hours of reperfusion. There was no difference in serum transaminase levels with AST 15113 +/- 4336 U/L (glutamine) vs. 17695 +/- 8531 U/L (control, P > 0.05), and ALT 7763 +/- 2524 (glutamine) U/L vs. 5884 +/- 2063 U/L (control, P > 0.05). The degree of neutrophil accumulation and necrosis was not different between groups at 24 hours of reperfusion. Pretreatment did not result in HSP70 upregulation in any of the groups. Pretreatment with glutamine did not reduce hepatic ischemia/reperfusion injury. The lack of protection was associated with an absence of HSP70 upregulation prior to ischemia.