Infant formulas (IFs) contain reduced cholesterol concentrations compared with breast milk (SM); how neonatal cholesterol metabolism responds to this difference is largely unknown. The effect of exclusive feeding of SM vs low-cholesterol IF on intestinal and hepatic cholesterol concentrations and synthesis during early postnatal development were compared in piglets. Animals were killed at birth or on days 5, 10, 15, or 25 postpartum. Plasma cholesterol concentrations were higher in SM-fed than in IF-fed piglets on days 15 and 25. In intestine both HMG-CoA reductase activity and 3H2O incorporation rates into cholesterol were similar for both groups or reduced in the IF-fed group at days 15 and 25. In liver, HMG-CoA reductase activity was higher in IF-fed than in SM-fed piglets on days 5, 10, and 15. Results indicate that during the early postpartum period, response to lower cholesterol intakes with IF occurs by increasing hepatic sterol synthesis whereas intestinal synthesis is largely unaffected.