There is evidence for an association between polymorphisms of serotonin- and dopamine-related genes and temperamental personality traits. Recent findings have shown that interactions between allelic variants of the different genes may contribute to personality traits. We examined the effects of serotonin transporter-linked promoter region (5-HTTLPR) and dopamine transporter (DAT1) gene polymorphisms for associations with the Temperament and Character Inventory (TCI) temperament subscales in 209 Koreans. We found that the variants of 5-HTTLPR interacted with the DAT1 gene polymorphism to influence the HA and RD temperament subscales of TCI. Neither of these two genes affected any subscales of TCI alone.Controlling for the effects of gender and age, we found significant interactions between 5-HTTLPR and DAT1 genes on Harm Avoidance (HA) and Reward Dependence (RD) as measured by the TCI (Hotelling's Trace = 3.0, P = 0.02). In the presence of the DAT1 10/10 genotype, subjects of group L of 5-HTTLPR had a significantly higher HA score and significantly lower RD score than those of group S (F = 5.04, df = 1, p = 0.03 and F = 8.35, df = 1, p = 0.004, respectively). These findings suggest that the variants of 5-HTTLPR interacted with the DAT1 gene polymorphism to influence the HA and RD temperament subscales of TCI.