Recent human functional imaging studies have linked the processing of pleasant visual stimuli to activity in mesolimbic reward structures. However, whether the activation is driven specifically by the pleasantness of the stimulus, or by its salience, is unresolved. Here we find in two studies that free viewing of pleasant images of erotic and romantic couples prompts clear, reliable increases in nucleus accumbens (NAc) and medial prefrontal cortex (mPFC) activity, whereas equally arousing (salient) unpleasant images, and neutral pictures, do not. These data suggest that in visual perception, the human NAc and mPFC are specifically reactive to pleasant, rewarding stimuli, and are not engaged during by unpleasant stimuli, despite high stimulus salience.