These present studies have identified some important differences between male and female subjects in ethanol pharmacokinetics. The development of alcohol misuse in female subjects clearly altered the rate of ethanol elimination as well as increasing the circulating levels of blood acetaldehyde. The identification of an increased level of acetaldehyde in subjects homogenous for ADH(3)(2) genotype, may in part contribute to the higher incidence of alcohol-related damage, i.e. liver cirrhosis, associated with this ADH(3) genotype. The enhanced presystemic alcohol metabolism identified in female Caucasian controls, but not female alcohol misusers, may be an important factor in removing a significant quantity of ethanol during its first pass through the liver and thereby reduce circulating acetaldehyde concentrations.