Prior work indicates that various aspects of task-irrelevant information (e.g. its salience, task-relatedness, emotionality) can increase the involvement of prefrontal cortex (PFC) in top-down attentional control. In light of these findings, we hypothesize that PFC’s involvement increases when task-irrelevant information competes for priority in processing. In an event-related fMRI study using an oddball variant of the Stroop task, we examine the generality of this hypothesis using three manipulations designed to increase the ability of task-irrelevant information to compete for priority in processing. First, we investigated how the frequency of occurrence of task-irrelevant information affects PFC activity. Second, we examined whether conflicting color information (i.e. incongruent trials) increases activity in regions of PFC that are similar to or distinct from those sensitive to infrequently occurring task-irrelevant information. Finally, we examined the impact of the number of levels at which conflict could occur (e.g. non-response only, non-response and response). Activity in posterior–dorsolateral and posterior–inferior PFC increased for infrequently occurring task-irrelevant information, being largest when the task-irrelevant information contained conflicting color-information. In contrast, increases in mid-dorsolateral prefrontal cortex’s activity were only noted when conflicting color information was present, being largest when conflict occurred at multiple levels. The anterior cingulate was primarily sensitive to the occurrence of conflict at the response level with only a small sub-region exhibiting sensitivity to non-response conflict as well. From these findings we suggest that posterior DLPFC and PIPFC are involved in biasing processing in posterior processing systems, mid-DLPFC is involved in biasing the processing of the contents of working memory, and ACC is primarily involved in response-related processes.