Interactive paradigms inducing reactive aggression are absent in the brain mapping literature. We used a competitive reaction time task to investigate brain regions involved in social interaction and reactive aggression in sixteen healthy male subjects with fMRI. Subjects were provoked by increasingly aversive stimuli and were given the opportunity to respond aggressively against their opponent by administering a stimulus as retaliation. fMRI revealed an increase of medial prefrontal cortex (mPFC) activity during retaliation. The dorsal mPFC was active when subjects had to select the intensity of the retaliation stimulus, and its activity correlated with the selected stimulus strength. In contrast, ventral mPFC was active during observing the opponent suffering but also during retaliation independent of the stimulus strength. Ventral mPFC activation, stronger in low callous subjects, correlated positively with skin conductance response during observation of the suffering opponent. In conclusion, dorsal mPFC activation seems to represent cognitive operations related to more intense social interaction processes whereas the ventral mPFC might be involved in affective processes associated with compassion to the suffering opponent.