Using positron emission tomography (PET) and [(11)C]raclopride, an association between striatal D(2) dopamine receptors and emotional detachment has been recently reported. Several laboratory findings indicate a link between the serotoninergic system and harm avoidance. In this study we investigated, in a group of healthy volunteers, the relationship between the in vivo binding of 3-(2'-[(18)F]fluoroethyl)spiperone ([(18)F]FESP) to cortical 5HT(2) and striatal D(2) receptors and three personality dimensions, i.e., "novelty seeking," "reward dependence," and "harm avoidance." Eleven healthy volunteers were evaluated by means of the Tridimensional personality Questionnaire (C. R., Arch. Gen. Psychiatry 44: 573-588.) and underwent a PET scan with [(18)F]FESP. Harm avoidance showed a significant inverse correlation with [(18)F]FESP binding in the cerebral cortex, particularly in the frontal cortex (R(2) = -0.709, P = 0.0145) and left parietal cortex (R = -0.629, P = 0.038) but not in the basal ganglia (r = -0.176, P = 0.651). Similar results were obtained using SPM at a P threshold of 0.05. No significant correlation was observed with novelty seeking or reward dependence. In the cerebral cortex, high values of [(18)F]FESP binding values are associated with a high tendency to avoid danger, indicating involvement of the serotoninergic system and, in particular, 5HT(2A) receptors, in this trait of personality. The results of this as well as of previous studies on personality dimensions indicate the existence of a relationship between behavioral and neurobiological factors. In addition these results support the concept that the variability of PET data may be explained by neurochemical differences related to the prevalence of specific personality traits.