The effect of allopurinol on protein synthesis, tissue water, and adenine nucleotides in liver tissue during and after a period of liver ischemia was investigated in rats. Ischemia was induced in the left and median liver lobes for 1 hour and experiments were continued for 2 hours after reperfusion. One group of animals (n = 20) received allopurinol (50 mg/kg body weight) intravenously 10 minutes before induction of liver ischemia. Control rats (n = 20) were given a corresponding volume of saline solution. Protein synthesis was measured by determining the rate of amino acid incorporation into protein in incubated liver slices. The reduction of protein synthesis and energy level in liver tissue and the increase of hepatic tissue water were similar in both groups of animals at the end of the ischemic period. During reperfusion the protein synthesis rate was higher and hepatic tissue water was lower in allopurinol-treated animals than in control rats. No significant differences in hepatic adenine nucleotides were found between the two groups of rats during ischemia or after reperfusion. The results demonstrated that improved protein synthesis and reduced tissue water in the postischemic liver after administration of allopurinol were not the result of improved restoration of adenine nucleotides. Inhibited production of oxygen-free radicals might be one mechanism by which allopurinol exerted its beneficial effect after liver ischemia.