Examined the cortical activity associated with personal involvement in social interaction. While fMRI data were recorded, 18 male subjects (mean age 26 years) watched a virtual scene of social interaction. The subjects were either looked at by one of the characters or observed him looking at someone else. Moreover, the virtual character showed either arbitrary facial movements or socially relevant facial expressions such as used in greetings. Cortical activity was stronger in the anterior medial prefrontal cortex when participants were gazed at, whereas there was more activity in the precuneus when they merely observed an interaction. Socially relevant facial expressions increased activity in the ventral medial prefrontal cortex, and arbitrary facial movements led to more activation of the middle temporal gyrus. It is concluded that different areas of the medial prefrontal cortex play differential roles in social cognition, with ventral areas supporting the analysis of interaction-relevant facial expressions and dorsal areas responsible for the detection of self-relevance in social interaction.