An expression profile of active genes in the human liver was obtained by collecting sequences with a 3'-directed cDNA library that faithfully represents composition of the mRNA population. The results show the relative activity of ca. 600 genes in maintaining the hepatocytes and sustaining their liver-specific phenotypes. The most active group of genes are those for the production of plasma proteins, followed by the genes for the synthesis of lipoproteins, protease inhibitors, coagulation factors, and complements. This balance of gene activity was maintained for four independently obtained expression profiles from human livers, including those of adult and fetus. The expression profiling was extended to the liver of adult mouse, used as a model for the molecular etiology of hepatocytes and for examining the effects of drugs. Subtle biological differences between the human and mouse livers are reflected in the global expression profiles of active genes, especially with regard to the synthesis of plasma proteins, lipoproteins and complements. This comparative analysis using expression profiling should find a wide application in comparative biology.