MAO-A and -B are key isoenzymes that degrade biogenic and dietary amines. MAO-A preferentially oxidizes 5-HT and NE, whereas MAO-B preferentially oxidizes PEA. However, the substrate and inhibitor selectivity overlap depending on the concentration of the enzyme and substrate. A line of transgenic mice has been generated in which the gene that encodes MAO-A is disrupted. MAO-A KO mice have elevated brain levels of 5-HT, NE and DA and manifest aggressive behavior similar to men with a deletion of MAO-A. We have also generated mice deficient in MAO-B by homologous recombination. Interestingly, MAO-B KO mice do not exhibit aggression and only levels of PEA are increased. MAO-B-deficient mice are resistant to the Parkinsongenic neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Thus, studies of MAO-A and -B KO mice have clearly shown that MAO-A and -B have distinct functions in neurotransmitter metabolism and behavior. MAO KO mice are valuable models for investigating the role of monoamines in aggression and neurodegenerative and stress-related disorders.