MAO (monoamine oxidase) A and B are key isoenzymes that degrade biogenic and dietary amines. MAO A preferentially oxidizes serotonin (5-hydroxytryptamine, 5-HT) and norepinephrine (NE), whereas MAO B preferentially oxidizes phenylethylamine (PEA). Both forms can oxidize dopamine (DA). However, the substrate specificity overlap and the in vivo function of these two isoenzymes is not clear. Recently, we have shown that MAO A and B knock-out (KO) mice exhibit distinct differences in neurotransmitter metabolism and behavior. 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. In contrast, MAO B KO mice do not exhibit aggression and only levels of PEA are increased. Both MAO A and B KO mice show increased reactivity to stress. Taken together, these results suggest that MAO A and B have distinctly different roles in monoamine metabolism. Further, these mice are valuable models for investigating the role of monoamines in psychoses and neurodegenerative and stress-related disorders.