Abstract It has become increasingly evident that one of the most fruitful approaches to understanding cellular processes and their relation to disease consists of large-scale gene profiling of cells, tissues, and organs. This also constitutes a first step in exploring the molecular biologic basis of various diseases. In the current study, we used cDNA microarray technology to assess possible changes in the expression of a large number of genes in the liver of rats fed alcohol (ethanol) chronically (4 weeks) by means of intragastric infusion. This animal model resembles closely the alcoholic liver disease in human beings. Of a total of 8,740 probe sets arrayed on the microchip, 2,069 were expressed by the liver. After a correction for false discovery rate at 10%, 72 genes were found to be significantly up-regulated (40) or down-regulated (32). Forty-two genes were suppressed, and four genes were induced, by alcohol. These genes are involved in a wide spectrum of cellular functions. Also, the genes that underwent significant changes were categorized into two groups: genes that have been implicated in alcoholic liver disease and genes that have not been tested for possible changes in expression. Large-scale gene profiling of the liver reveals changes in the expression of a number of genes that have never been implicated in alcohol-induced injury. Further investigation of such genes may cast light on mechanisms underlying alcohol-induced liver injury and help in the design of new therapeutic approaches.