Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are the major enzymes responsible for the metabolism of alcohols and aldehydes in the body. Both exist as a family of isozymes in mammals, and have been extensively studied in animal models, particularly among inbred strains of mice. Mouse ADH exists as at least three major classes, which are predominantly localized in liver (classes I and III), and in stomach/cornea (class IV). Mouse ALDH exhibits extensive multiplicity, several forms of which have been characterized, including ALDH1 (liver cytoplasmic/class 1 isozyme); ALDH2 (liver mitochondrial/class 2.); ALDH3 (stomach cytosolic/class 3); ALDH4 (liver microsomal/class 3); and ALDH5 (testis cytosolic/class 3). Biochemical, genetic and molecular genetic analyses have been performed on several of these enzymes, including studies on variant forms of ADH and ALDH. Distinct metabolic roles are proposed, based upon their tissue and subcellular distribution characteristics and the biochemical properties for these enzymes.