Monoamine oxidase (MAO) activity was determined in blood from 113 normal subjects ranging from 21 to 84 years of age and in hindbrain obtained at autopsy from 26 patients. MAO activity correlated highly with increasing age for all three sources of enzyme studied (hindbrain, plasma, and platelets). Women were found to have significantly higher mean platelet and plasma MAO activity than men. The tendency for greater MAO activity in women and with aging is intriguing because it is consistent with clinical observations about the incidence of depressive illness. Increased enzyme activity related to aging and sex may be a biologic factor that, in association with Psychological and social stresses, predisposes certain individuals to the development of depression.