Mediating proactive interference (PI), the deleterious effect of antecedent information on current memory representations, is believed to be a key function of prefrontal cortex (PFC). Item-specific PI results when an invalid probe matches a memorandum from the preceding trial; item-nonspecific PI is produced by the accumulation of no-longer-relevant items from previous trials. We tested the hypothesis that these two types of PI are mediated by common PFC-based processes with an fMRI study of a delayed-recognition task designed to produce both types of PI. Our results indicated that the fMRI correlates of both effects were restricted both to Brodmann's area 45 in the left hemisphere and to the memory probe epoch of the trial. These results suggest that a unification of the literatures and approaches that have independently studied these phenomena might offer a fruitful new perspective from which to study the relations between working memory, executive control, and the PFC.