Previous theories have proposed that the amygdala is hyper-responsive to novel stimuli in persons with an inhibited temperament-a biologically based predisposition to respond to novelty with wariness or avoidance behavior. In the current study, we used functional magnetic resonance imaging (fMRI) to assess amygdala blood oxygenation level-dependent (BOLD) response when viewing novel or recently familiarized faces in persons with an extreme inhibited or uninhibited temperament. In persons with an inhibited temperament, the amygdala showed increased BOLD response when viewing both novel and recently familiarized faces. In contrast, in persons with an uninhibited temperament, BOLD response in the amygdala was increased only when viewing novel faces. These findings suggest that inhibited temperament is characterized not by a simple exaggerated response to novel faces, but rather by a sustained increase in amygdala response to faces even after the faces have become familiarized. In individuals with an inhibited temperament, this sustained response may be related to the wariness of social situations that persists beyond initial exposure.