The activities of hexokinase, glucose-6-phosphate dehydrogenase, and glycolytic enzymes were higher in the fetal myocardium of the guinea pig than at birth and fell progressively during the 1st mo of life. The alphaHBDH/LDH ratio of H to M subunits of lactate dehydrogenase, was low in the fetus and continued to rise during the 1st mo after birth. The distinction between the left and right ventricular activities of lactate dehydrogenase, which is clear in adult guinea pigs, was absent in the fetus and appeared during postnatal development. Glycogen phosphorylase activity was low in the fetus and at birth. The activities of beta-hydroxyacylcoenzyme A dehydrogenase, succinate dehydrogenase, malate dehydrogenase, and aspartate aminotransferase were low in the fetus, but had reached, or even temporarily exceeded, normal adult levels at birth. Palmitylcarnitine transferase activity was also low in the fetal heart compared with the newborn but continued to increase substantially during the first 2 wk after birth.