Two hundred male subjects (81 college students and 119 subjects from an addiction treatment unit) were administered the Temperament and Character Inventory (TCI) and genotyped at the 48 base pair repeat polymorphism of the DRD4 gene. Subjects were divided by genotype into those carrying any < 4 repeat allele, those homozygous for the 4 repeat allele, and those with any > 4 repeat allele. The total MANCOVA of seven TCI summary scores, with age and diagnostic group as covariates, was significant (P < or = 0.001). The largest effect was with self-transcendence (P < or = 0.001). The total MANCOVA for the three self-transcendence subscores was significant (P < or = 0.017), with the spiritual acceptance subscore showing the most effect (P < or = 0.001, power = 0.91). These results suggest the DRD4 gene may play a role in the personality trait of spiritual acceptance. This may be a function of the high concentration of the dopamine D4 receptor in the cortical areas, especially the frontal cortex.