Meal-fed Long-Evans rats fed a high fructose diet and exercised for 2-hr daily on a treadmill for three days had lower levels of several hepatic lipogenic enzymes (acetyl CoA carboxylase, glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, malic enzyme and citrate cleavage enzyme) than did sedentary rats pair-fed the diet. Accumulation of triglycerides in plasma following ingestion of a fat-free, high fructose meal and injection of Triton WR-1339, an inhibitor of plasma triglyceride clearance, was not significantly different in the two groups of animals. All of the hepatic lipogenic enzymes measured, with the exception of citrate cleavage enzyme, attained similar levels in the runners as in the controls after 5 days on the high fructose diet. Thus the exercise appeared to affect the time course of the increase in the levels of activity of most of the lipogenic enzymes but not the final steady state levels attained.