To investigate the gene expression profile of a normal human liver, we performed serial analysis of gene expression (SAGE), which allows the quantitative and simultaneous analysis of thousands of genes expressed in tissue. Polyadenylated RNA was obtained from a hulk normal human liver sample and SAGE was performed. Reverse transcriptase-polymerase chain reaction (RT-PCR) was also performed in each of 3 different normal liver samples to evaluate the validity of the profile in each individual. A total of 30,982 tags were sequenced, 8,596 of which were unique. The genes highly expressed in the normal Liver were those encoding plasma proteins (>21.8% of total transcripts), cytoplasmic proteins (>8.6%), enzymes (>4.8%), protease inhibitors (>1.7%), complements (>1.1%), and coagulation factors (>0.75%). About 13.9% of all transcripts encoded genes not reported in GenBank thus far. This study identifies candidate genes to be examined in relation to various human liver diseases, including viral hepatitis, liver cirrhosis, and hepatocellular carcinoma.