Rat hepatic mitochondrial hydroxymethylglutaryl-CoA (HMG-CoA) synthase activity increases throughout the perinatal period, indicating that the factors necessary for the induction of the enzyme are present in utero. Reciprocal changes occur in 3-ketoacid transferase activity during late fetal life, suggesting that ketone body formation and utilization may be subject to coordinate regulation. Cytosolic HMG-CoA synthase activity is low during fetal life and rises rapidly after birth. The activities of both cytosolic and mitochondrial enzymes in fetal liver are dependent upon maternal diet and different dietary effects are observed at different fetal ages.