Hepatocytes from the periportal (afferent) and perivenous (efferent) zones of the liver parenchyma differ in their enzyme content and subcellular structures. Therefore, different functions are proposed for the two zones. (a) Oxidative energy metabolism, beta-oxidation, amino acid catabolism, ureagenesis from amino acids, gluconeogenesis, bile acid, and bilirubin excretion and oxidation protection are preferentially located in the periportal zone. (b) Glycolysis, liponeogenesis, ureagenesis from ammonia, and biotransformation are predominantly situated in the perivenous zone. Heterogeneity in the synthesis of plasma proteins also appears to exist. The heterogeneous expression of the genome in hepatocytes is apparently caused by the periportal to perivenous gradient in oxygen and hormone concentrations, and by a different autonomic innervation of the parenchymal zones.