Goal-directed behaviour depends on keeping relevant information in mind (working memory) and irrelevant information out of mind (behavioural inhibition or interference resolution). Prefrontal cortex is essential for working memory and for interference resolution, but it is unknown whether these two mental abilities are mediated by common or distinct prefrontal regions. To address this question, functional MRI was used to identify brain regions activated by separate manipulations of working memory load and interference within a single task (the Sternberg item recognition paradigm). Both load and interference manipulations were associated with performance decrements. Subjects were unaware of the interference manipulation. There was a high degree of overlap between the regions activated by load and interference, which included bilateral ventrolateral and dorsolateral prefrontal cortex, anterior insula, anterior cingulate and parietal cortex. Critically, no region was activated exclusively by interference. Several regions within this common network exhibited a brain-behaviour correlation across subjects for the load or interference manipulation. Activation within the right middle frontal gyrus and left inferior frontal gyrus was correlated with the ability to resolve interference efficiently, but not the ability to manage an increased working memory load efficiently. Conversely, activation of the anterior cingulate was correlated with load susceptibility, but was not correlated with interference susceptibility. These findings suggest that, within the circuitry engaged by this task, some regions are more critically involved in the resolution of interference whereas others are more involved in the resolution of an increase in load. The anterior cingulate was engaged to a greater extent by the load than interference manipulation, suggesting that this region, which is thought to be involved in detecting the need for greater allocation of attentional resources, may be particularly implicated during awareness of the need for cognitive control. In the present study, interference resolution did not involve recruitment of additional inhibitory circuitry, but was instead mediated by a subset of the neural system supporting working memory.