Gaze direction is known to be an important factor in regulating social interaction. Recent evidence suggests that direct and averted gaze can signal the sender's motivational tendencies of approach and avoidance, respectively. We aimed at determining whether seeing another person's direct vs. averted gaze has an influence on the observer's neural approach-avoidance responses. We also examined whether it would make a difference if the participants were looking at the face of a real person or a picture. Measurements of hemispheric asymmetry in the frontal electroencephalographic activity indicated that another person's direct gaze elicited a relative left-sided frontal EEG activation (indicative of a tendency to approach), whereas averted gaze activated right-sided asymmetry (indicative of avoidance). Skin conductance responses were larger to faces than to control objects and to direct relative to averted gaze, indicating that faces, in general, and faces with direct gaze, in particular, elicited more intense autonomic activation and strength of the motivational tendencies than did control stimuli. Gaze direction also influenced subjective ratings of emotional arousal and valence. However, all these effects were observed only when participants were facing a real person, not when looking at a picture of a face. This finding was suggested to be due to the motivational responses to gaze direction being activated in the context of enhanced self-awareness by the presence of another person. The present results, thus, provide direct evidence that eye contact and gaze aversion between two persons influence the neural mechanisms regulating basic motivational-emotional responses and differentially activate the motivational approach-avoidance brain systems.