Different gene variants may exert complex effects on human behavior. A group of healthy Bulgarian subjects (n=144, females= 62%, males=38%) was assessed by the Cloninger's Temperament and Character Inventory (TCI) and genotyped for 7 polymorphisms. We focused on polymorphisms in genes of the serotoninergic and dopaminergic neurotransmitter systems, and in enzymes mediating the metabolism of endogenous amines within the brain. An association was tested between the TCI performance and -1438G/A polymorphism in the HTR2A gene, Cys23Ser in 5-HT2C gene, two 5-HTT polymorphisms (ins/del 5-HTT-PR and the intron 2 VNTR), the 3'UTR VNTR in DAT1 gene, Val158Met in COMT and 3'VNTR in the MAOA gene. Linear regression was utilized, controlling for gender effects. It was found that the low activity met158 variant of COMT is more common among people with low scores on reward dependence (F=2.595, df=8, p=0.012), self directness (F=2.357, df=8, p=0.022) and cooperativeness (F=3.75 1, df=8, p=0.001). A trend of association between homozygosity for the short MAOA allele and low performance for the TCI subscale cooperativeness was found (B=-11.56 SE= 5.75, p=0.047). Individuals with 10/10 DAT genotype were more likely to have higher persistence scores than the others (B=24.16, SE=8.96, p=0.008). The presence of HTR2A-pr allele 2 was associated with low Self-Transcendence (B=-19.65 SE=6.66 p=0.004). The results of our study delineate some polymorphic variants of enzyme and transporter genes with possible contribution to character and temperament in healthy Bulgarian subjects. Additional studies in larger sample to confirm the findings and determine possible epigenetic interactions are warranted.