The personality trait Openness/Intellect reflects the tendency to be imaginative, curious, perceptive, artistic, and intellectual-all characteristics that involve cognitive exploration. Little is known about the biological basis of Openness/Intellect, but the trait has been linked to cognitive functions of prefrontal cortex, and the neurotransmitter dopamine plays a key role in motivation to explore. The hypothesis that dopamine is involved in Openness/Intellect was supported by examining its association with two genes that are central components of the prefrontal dopaminergic system. In two demographically different samples (children: N = 608; adults: N = 214), variation in the dopamine D4 receptor gene (DRD4) and the catechol-O-methyltransferase gene (COMT) predicted Openness/Intellect, as main effects in the child sample and in interaction in adults.