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In several twin studies the relative contribution of genetic factors for personality traits has amounted to figures between 40 and 60%. In the present study we investigated to which degree polymorphisms in the 5-HTT and AP-2 beta genes are implicated in the neural processes involved in the formation of Temperament and Character traits, as estimated by Cloninger's TCI. Considering the background of previous reports, associations with the character Self-Transcendence and its sub-scale Spiritual Acceptance in particular, were of interest. A stratified random sample of 200 individuals (total population = 5173), matched for age, gender and risk behaviors, from volunteering 16- and 19-year-old adolescents students in Sweden was investigated. Cloninger's TCI inventory was used for investigation of temperament and character traits. Blood samples were used for analyses of a promoter serotonin transporter polymorphism (5-HTTLPR) and an intron 2 polymorphism in the transcription factor AP-2 beta gene. Among boys individuals with presence of the short 5-HTTLPR genotype showed lower scores, whereas individuals with presence of the short AP-2 beta genotype showed higher scores of personality character Self-Transcendence and its sub-scale Spiritual Acceptance. Among girls no effect of either genotype was found. Both among boys and girls, significant interactive effects were found between 5-HTTLPR and AP-2 beta genotypes, with regard to Self-Transcendence and Spiritual acceptance. Boys and girls with the combination of presence of the short 5-HTTLPR, and homozygosity for the long AP-2 beta genotype scored significantly lower on Self-Transcendence and Spiritual Acceptance.