Several functionally connected networks of activity have now been identified in the resting human brain that may be amplified or attenuated by specific goal-directed tasks. However, it is not known whether there exists a particular network that becomes more active when a person is engaged in a social interaction. fMRI was used to measure brain activity in subjects as they completed a social interactive task and a non-social control task sharing many of the same features. Comparison across the two tasks revealed a network of functionally connected areas that was consistently more active in the social task. This network included default mode network areas, raising the possibility that activity previously observed in default mode regions at rest is related to social cognition. Within this network, information appears to flow from regions involved in salience detection (e.g. anterior insula) to regions involved in mentalizing (dorsomedial prefrontal cortex) to regions involved in executive control (dorsolateral prefrontal cortex). In a second experiment, subjects played the same social interactive task with alleged members of both an experimentally induced in-group and out-group. The default mode network was again active during the task, and several noteworthy differences distinguished interactions with in-group and out-group partners, providing a potential neural substrate for the human tendency to more readily identify with in-group members and more readily distrust, fear and discriminate against out-group members.