Background: Convergent evidence suggests dysfunction within the prefrontal cortex (PFC) and amygdala, important components of a neural system that subserves emotional processing, in individuals with major depressive disorder (MDD). Abnormalities in this system in the left hemisphere and during processing of negative emotional stimuli are especially implicated. In this study, we used functional magnetic resonance imaging (fMRI) to investigate amygdala-PFC functional connectivity during emotional face processing in medication-naive individ - uals with MDD. Methods: Individuals with MDD and healthy controls underwent fMRI scanning while processing 3 types of emotional face stimuli. We compared the strength of functional connectivity from the amygdala between the MDD and control groups. Results: Our study included 28 individuals with MDD and 30 controls. Decreased amygdala-left rostral PFC (rPFC) functional connectivity was observed in the MDD group compared with controls for the fear condition (p < 0.05, corrected). No significant differences were found in amygdala connectivity to any cerebral regions between the MDD and control groups for the happy or neutral conditions. Limitations: All participants with MDD were experiencing acute episodes, therefore the findings could not be generalized to the entire MDD population. Conclusion: Medicationnaive individuals with MDD showed decreased amygdala-left rPFC functional connectivity in response to negative emotional stimuli, suggesting that abnormalities in amygdala-left rPFC neural circuitry responses to negative emotional stimuli might play an important role in the pathophysiology of MDD.