Using event-related functional magnetic resonance imaging (fMRI), we examined the blood oxygen level-dependent response associated with intentional remembering and forgetting. In an item-method directed forgetting paradigm, participants were presented with words, one at a time, each of which was followed after a brief delay by an instruction to Remember or Forget. Behavioral data revealed a directed forgetting effect: greater recognition of to-be-remembered than to-be-forgotten words. We used this behavioral recognition data to sort the fMRI data into 4 conditions based on the combination of memory instruction and behavioral outcome. When contrasted with unintentional forgetting, intentional forgetting was associated with increased activity in hippocampus (Broadmann area [BA] 35) and superior frontal gyrus (BA10/11); when contrasted with intentional remembering, intentional forgetting was associated with activity in medial frontal gyrus (BA10), middle temporal gyrus (BA21), parahippocampal gyrus (BA34 and 35), and cingulate gyrus (BA31). Thus, intentional forgetting depends on neural structures distinct from those involved in unintentional forgetting and intentional remembering. These results challenge the standard selective rehearsal account of item-method directed forgetting and suggest that frontal control processes may be critical for directed forgetting.