Self-recognition has been demonstrated by a select number of primate species and is often used as an index of self-awareness. Whether a specialized neural mechanism for self-face recognition in humans exists remains unclear. We used event-related fMRI to investigate bra in regions selectively activated by images of one's own face. Ten right-handed normal subjects viewed digital morphs between their own face and a gender-matched familiar other presented in a random sequence. Subjects were instructed to press a button with the right hand if the image looked like their own face, and another button if it looked like a familiar or scrambled face. Contrasting the trials in which images contain more "self" with those containing more familiar "other" revealed signal changes in the right hemisphere (RH) including the inferior parietal lobule, inferior frontal gyrus, and inferior occipital gyros. The opposite contrast revealed voxels with higher signal intensity for images of "other" than for "self" in the medial prefrontal cortex and precuneus. Additional contrasts against baseline revealed that activity in the "self" minus "other" contrasts represent signal increases compared to baseline (null events) in "self" trials, while activity in the "other" minus "self" contrasts represent deactivations relative to baseline during "self" trials. Thus, a unique network involving frontoparietal structures described as part of the "mirror neuron systern" in the RH underlies self-face recognition, while regions comprising the "default/resting state" network deactivate less for familiar others. We provide a model that reconciles these findings and previously published work to account for the modulations in these two networks previously implicated in social cognition. (c) 2004 Elsevier Inc. All rights reserved.