This study examined the relationship between alcohol/illicit drug use, the Five-Factor Model (FFM) personality traits, aggressiveness (Agg), and hyperactivity (Hyp), and platelet monoamine oxidase (MAO) activity in a population-derived representative sample of preadolescents and adolescents (n=1172). Alcohol and illicit drug use was self-reported. The FFM personality inventories were filled in by mothers of the participants, and Agg and Hyp were rated by their class teachers. Higher scores in extraversion (E), Agg, and Hyp and lower scores in conscientiousness (C) together with older age were significant predictors of more frequent alcohol use in adolescents. No significant association was found between alcohol illicit drug use, and platelet MAO activity.