Abstract Amygdala reactivity is a heritable trait, potentiated in affective disorders and associated with both the 5-HTTLPR and the COMTval158met polymorphism. Fifty-four healthy volunteers selected a priori based on gender and 5-HTTLPR/rs25531 and COMTval158met genotypes performed a passive viewing task of angry facial expressions using fMRI. Amygdala reactivity and habituation were investigated using the a priori anatomical region of interest (ROI) approach. Furthermore, salivary cortisol and skin conductance responses were recorded. We observed an effect of 5-HTTLPR on right amygdala reactivity (s-carrier > l/l) and COMTval158met on left amygdala reactivity (met/met > val-carrier). We provide preliminary evidence that different amygdala habituation curves may partly underlie the differences between 5-HTTLPR and not COMT genotype groups. Further, exploratory analyses find no evidence for additive or interaction effects. Our results support that 5-HTTLPR s-carriers and COMT met/met carriers may be more sensitive to the detection of biologically and socially relevant information and suggest a mechanism behind this for the 5-HTTLPR.