Neuroimaging has revealed consistent activations in medial prefrontal cortex (MPFC) and posterior cingulate cortex (PCC) extending to precuneus both during explicit self-reference tasks and during rest, a period during which some form of self-reference is assumed to occur in the default mode of brain function. The similarity between these two patterns of midline cortical activation may reflect a common neural system for explicit and default-mode self-reference, but there is little direct evidence about the similarities and differences between the neural systems that mediate explicit self-reference versus default-mode self-reference during rest. In two experiments, we compared directly the brain regions activated by explicit self-reference during judgments about trait adjectives and by rest conditions relative to a semantic task without self-reference. Explicit self-reference preferentially engaged dorsal MPFC, rest preferentially engaged precuneus, and both self-reference and rest commonly engaged ventral MPFC and PCC. These findings indicate that there are both associations (shared components) and dissociations between the neural systems underlying explicit self-reference and the default mode of brain function. Copyright © 2010 Elsevier Inc. All rights reserved.