The role of gender as a variable that might affect the metabolism of ethanol and thus the hepatotoxicity of ethanol is evaluated. First, the pharmacodynamics of ethanol are reviewed with particular attention to hormone effects on ethanol absorption and metabolism. Specific differences between males and females relative to ethanol pharmacokinetic parameters are discussed, including gender differences in the volume of distribution and putative hormonal effects on achieved blood alcohol levels. In addition, attention is directed toward the metabolic capacity of alcohol dehydrogenase and the microsomal ethanol-oxidizing system with respect to effects of both sex differences and hormonal manipulations on the activity of these ethanol-metabolizing enzymes. Finally, the studies on the concept of sex-related differences in susceptibility to alcohol hepatotoxicity are examined.