The purpose of this study was to investigate the effects of the 5-HTTLPR and brain-derived neurotrophic factor (BDNF) Val66Met polymorphisms on self-reported Big Five personality traits and their facets in a population representative sample of adolescents. The sample consisted of both cohorts of the Estonian Children Personality Behaviour and Health Study, and personality data were collected during its second waves. The 5-HTTLPR and BDNF Val66Met polymorphisms were genotyped. The BDNF Val66Met had a significant effect on conscientiousness [F(1,807)=4.32, P=0.038]. We did not find effects of the 5-HTTLPR polymorphism on the main domains of personality, however, a gene×gene interaction on conscientiousness emerged -BDNF Val66Met Met-allele carriers with the 5-HTTLPR s/s genotype had by far the lowest scores in conscientiousness [F(2,803)=4.38, P=0.012]. In addition, we found genotype effects on some facet scales. In conclusion, the BDNF Val66Met genotype Met-allele carriers have lower conscientiousness, and this effect is increased in the 5-HTTLPR s/s individuals.