Friendships form one of the most proximal contexts with a critical role in mental health and social and psychological development. Yet, the neurobiological basis of this crucial developmental factor is largely uninvestigated. In this study, we tested the hypothesis that the interaction with friends is associated with specific activity increases in brain areas known to be involved in interpersonal phenomena, such as empathy, and in reward expectancy. Using functional magnetic resonance imaging (fMRI), we assessed neural activity in a social interaction simulation task implementing the factors 'type of relationship' (peers vs. familiar celebrities) and 'emotional valence' (positive (liked), negative (disliked), and neutral (neither liked nor disliked)). In this design, all stimuli were selected individually for each of the 28 participants and positive peers constituted the friends. Participants were asked to approach a stimulus, to avoid it, or remain neutral. Behavioral results confirmed the expectations in the sense that the participants approached positive stimuli more often than they approached neutral, which were also more often approached than negative stimuli. Moreover, peers were more often approached than celebrities were. Imaging results revealed, among others, three regions of particular interest as selectively more strongly activated when subjects interacted with their friends than with other peers and celebrities: the amygdala and hippocampus, the nucleus accumbens, and the ventro-medial prefrontal cortex. These results might highlight the role of empathy and reward-related processes in friendship. Thus, we may have identified a potential mechanism by which friendships exert such a critical role in development and mental health.