Humans are remarkably accurate at recognizing familiar faces, whereas their ability to recognize, or even match, unfamiliar faces is much poorer. However, previous research has failed to identify neural correlates of this striking behavioral difference. Here, we found a clear difference in brain potentials elicited by highly familiar faces versus unfamiliar faces. This effect starts 200 ms after stimulus onset and reaches its maximum at 400 to 600 ms. This sustained-familiarity effect was substantially larger than previous candidates for a neural familiarity marker and was detected in almost all participants, representing a reliable index of high familiarity. Whereas its scalp distribution was consistent with a generator in the ventral visual pathway, its modulation by repetition and degree of familiarity suggests an integration of affective and visual information.