In 1981, a comprehensive article on the metabolism and metabolic effects of ethanol1 appcarcd in Seminars in Liver Disease and summarized the evidence that had accumulated on the hepatotoxicity of ethanol and on some of the mechanisms involved. Since then, considerable progress has been made, to be summarized here. In addition to the clarification of some metabolic changes related to the oxidation of ethanol via the alcohol dehydrogenase (ADH) pathway, major insight was gained into the intemction of ethanol with various xenobiotic agents on the basis of the elucidation ot a pathway for ethanol metabolism, the microsomal ethanol oxidizing system (MEOS) involving a new, cthiinol-spccific form of cytochrome P450 (P45011E1). Figure 1 lists a number of ethanol-related hepatic effects and their relationship either to ADH-mcdiated generation of reduced nicotinamide adenine dinucleotide (NADH) the induction of MEOS, or the product of both pathways, namely acetaldehyde. Much of the progress achieved was made possible through the development of adequate experimental models (Table 1).