The effect of diet type and feeding status on hepatic HMG-CoA reductase (HMGR) [mevalonate: NADP+ oxidoreductase (acylating CoA); EC 1.1.1.34] was studied in rats. Animals fed a ground, commercial, stock diet exhibited higher expressed and total activities of HMGR in the fed state than animals fed a semi-purified diet. The differences did not appear in meal-trained animals when measured before the onset of the meal after a 22-hr fast. When expressed activity was taken as a per cent of total activity, fed animals from both diet groups used about 10% of their available activity. When animals on commercial diets were fasted, 20% of the activity was expressed. Fasted animals on the semi-purified diet also increased the per cent of expressed reductase activity, but this increase was not as great (13.3%). These data suggest that, in the rat, regulation of cholesterol synthesis in response to decreased total HMGR during fasting and increased levels after a meal results from alterations in the percentage of enzyme which is expressed. The semi-purified diet used here resulted in consistently lower levels of HMG-CoA reductase activity than the commercial diet regardless of feeding pattern.