The liver has a multitude of functions. First, the liver is the center of metabolism. It has a key position, on the one hand, in the maintenance of the energy supply of the organism, for example: after a normal carbohydrate-rich meal it takes up excess glucose and in between meals it liberates glucose; it synthesizes ketone bodies; it is the main organ of amino acid utilization; it is the major site for the removal of ammonia by forming urea and glutamine: and it processes nutrient triglycerides and adipose tissue-derived fatty acids. On the other hand, the liver is responsible for the synthesis and degradation of many essential compounds. In this regard it holds a key position in the metabolism of phospholipids and cholesterol, that is, of lipoproteins; it is the major site for the synthesis and degradation of plasma proteins; it forms bile; and it is the main organ of biochemical defense transforming xenobiotics into excretable derivatives. Second, the liver is a major control station in the hormonal system: it contributes to the maintenance of the peripheral levels of hormones by degrading almost all of them during a single passage; it forms and releases signal substances. Finally, the liver stores blood both actively and passively. These manifold functions are provided by the parenchymal and the nonparenchymal cells of the organ. All cell types are under the control of the substrate and hormone concentrations in blood, the autonomic innervation, and the biomatrix; the parenchymal and the nonparenchymal cells can be controlled also by mutual interactions. Moreover, an important factor is the zonal heterogeneity of the parenchymal cells. This article attempts to give a short overview on the present knowledge of parenchymal heterogeneity and, thereby, to improve the understanding of liver functions in normal and pathologic states. Functional hepatocyte heterogeneity has been reviewed recently both in genera11p2 and in parti~ ular,~-~ focusing on the metabolism of carbohydrate~,~.~ lipid^,^ amino acids and arn~ nonia,~.~ xenobioti~ s,~ or bile acids. 9