Background: The broad autism phenotype includes subclinical autistic characteristics found to have a higher prevalence in unaffected family members of individuals with autism. These characteristics primarily affect the social aspects of language, communication, and human interaction. The current research focuses on possible neurobehavioral characteristics associated with the broad autism phenotype. Methods: We used a face-processing task associated with atypical patterns of gaze fixation and brain function in autism while collecting brain functional magnetic resonance imaging (fMRI) and eye tracking in unaffected (...) siblings of individuals with autism. Results: We found robust differences in gaze fixation and brain function in response to images of human faces in unaffected siblings compared with typically developing control individuals. The siblings’ gaze fixations and brain activation patterns during the face processing task were similar to that of the autism group and showed decreased gaze fixation along with diminished fusiform activation compared with the control group. Furthermore, amygdala volume in the siblings was similar to the autism group and was significantly reduced compared with the control group. Conclusions: Together, these findings provide compelling evidence for differences in social/emotional processing and underlying neural circuitry in siblings of individuals with autism, supporting the notion of unique endophenotypes associated with the broad autism phenotype. (shrink)