Background: depression is characterized by a stable negative bias toward emotional stimuli. This bias is associated with abnormal activities in emotion-processing regions (such as the amygdala) and cognitive-control regions (such as the dorsolateral prefrontal cortex [DLPFC]). However, it remains unclear whether the emotion-processing and cognitive-control regions affect negative cognitive bias independently or reciprocally. Experimental procedure: a functional magnetic resonance imaging (fMRI) study of 16 depressed patients and 16 matched control subjects was conducted during an emotion-interference task. Results: the accuracies were significantly lower in the depressed group than in the control group when subjects attended to the happy and the neutral faces. Compared with control participants, depressed patients showed abnormal activity in bilateral amygdala and the right DLPFC. In addition, a significant correlation was found between the right amygdala and the right DLPFC when subjects observed the happy faces. Conclusions: the results suggest that the dysfunction in positive emotion-processing and cognitive-control regions may reciprocally affect negative cognitive bias. Additionally, altered positive emotional interference processing in the fronto-limbic brain circuitry might be another cause of negative cognitive bias that finally leads to depression. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.