We administered the Karolinska Scales of Personality to 225 healthy subjects in Spain selected from a group of 925 individuals previously phenotyped with regard to their capacity to hydroxylate debrisoquine. A significant relationship was found between the scores in as many as 4 of the 15 subscales (psychic anxiety, psychasthenia, inhibition of aggression and socialization) and the debrisoquine hydroxylation capacity. Poor metabolizers were more anxiety-prone and less successfully socialized than extensive metabolizers of debrisoquine. This and a previous study among subjects in Sweden suggest that there may be a relationship between personality and the activity of the enzyme hydroxylating debrisoquine (cytochrome P4502D6). This polymorphic enzyme may have an endogenous neuroactive substrate or product, such as a biogenic neurotransmitter amine.