Introduction: Recently, human studies using exposure therapy to treat anxiety have demonstrated that pretreatment with D-cycloserine (DCS) enhances fear reduction in anxiety disorders. However, the underlying brain mechanisms mediating this fear reduction have yet to be determined. Methods: The effects of orally administered DCS on amygdala activity during the processing of repeated facial expressions were examined in this double-blind study. Fourteen healthy males (30.0±8.7 years of age) randomly received DCS 500 mg or placebo prior to 3.0 Tesla functional magnetic resonance imaging acquisition. All participants viewed four separate runs, consisting of a single block of a repeated facial expression (happy or fearful) bracketed by fixation blocks. Results: Anatomic region-of-interest analyses showed that the placebo group exhibited amygdala activation and response habitation, while the DCS group displayed blunted amygdala responses to emotional faces across the experiment, whereby habituation was not detected. Conclusion: This finding may have relevance for testing treatments of anxiety and depression.