The effect of the hypolipidemic agent AY-25,712 on liver catalase and carnitine acetyltransferase was studied in rats. At 250 mg/kg/day for 2 or 4 weeks, i.e., at least 125 times the minimum effective hypolipidemic dose, AY-25,712 had no effect on liver weight or liver catalase. Liver catalase was elevated after a 2-week treatment with clofibrate (+ 30%), bezafibrate (+71%), and fenofibrate (+77%) at doses of 250 mg/kg/day, and with ciprofibrate (+111%) at 25 mg/kg/day. Gemfibrozil at 250 mg/kg/day for 4 weeks increased catalase by 86%. The relative increase in liver weight induced by these compounds showed a good correlation to increased catalase. Nicotinic acid (250 mg/kg/day for 2 weeks) did not alter liver weight or catalase. Clofibrate increased carnitine acetyltransferase by 176% while AY-25,712 had no effect. The results show that AY-25,712 and nicotinic acid did not induce changes in the livers of rats which are associated with treatment by various other hypolipidemic agents.