Hydroxymethylglutaryl-coenzyme A (HMG-CoA) synthase is present in the mucosa of the proximal small intestine of the suckling rat, as are acetoacetyl-CoA thiolase and HMG-CoA lyase. At weaning the activity of HMG-CoA synthase decreases by 90%. This change in activity parallels a change in the rate of ketogenesis in vitro by mucosal scrapings. Starvation of the pups decreases the rate of ketogenesis. It is concluded that the mucosa of the developing rat has an active HMG-CoA pathway and that there may be a relationship between intestinal ketogenesis and milk consumption in the suckling rat. The possible physiological significance of this finding is discussed.