Facilitation of social attraction and bonding by the evolutionarily conserved neuropeptide oxytocin is well-established in female mammals. However, accumulating behavioral evidence suggests that oxytocin may have evolved sex-specific functional roles in the domain of human social cognition. A critical question is how oxytocin differentially modulates neural processing of social information in men and women, leading to divergent behavioral responses. Here we show that intranasal oxytocin treatment produces sex-and valence-dependent increases in amygdala activation when women view individuals identified as praising others but in men those who criticize them. Women subsequently show increased liking for the faces of these individuals, whereas in men it is reduced. Thus, oxytocin may act differentially via the amygdala to enhance the salience of positive social attributes in women but negative ones in men. We hypothesize that oxytocin may have evolved different but complementary roles to help ensure successful reproduction by encouraging mothers to promote a prosocial rearing environment for offspring and fathers to protect against antisocial influences.T he hypothalamic neuropeptide oxytocin (OXT) plays a key role in promoting maternal behavior and mother-infant bonding in mammals (1) as well as pair bonds with males in monogamous species (2). Recent studies in both monkeys and humans have suggested that it has not only evolved a more extensive role in social cognition in female primates but also become progressively used by males in this domain (3). Although OXT appears to facilitate both salience and motivational aspects of social cues in both sexes (3, 4), there is increasing evidence that it may often produce opposite effects in these domains in men and women (5-7), raising the intriguing possibility that it has evolved some sex-specific functions at both neural and behavioral levels. In particular, behavioral studies have reported that whereas OXT tends to facilitate positive social judgments (7), social approach (8), kinship recognition (5), and altruism (9) in women, in men it can facilitate negative social judgments (7), social avoidance (10), competitor recognition (5), and selfishness (9). Similarly, in response to couple conflict, OXT decreased sympathetic activity and arousal in women but increased them in men (6). The neural basis of these opposing sex-dependent behavioral effects of OXT has not, however, been established.Previous research has shown that the amygdala has different responses to positive and negative valence social information in men and women (11) and also may be a critical target for sex-specific functional effects of OXT. The amygdala has a sexually dimorphic distribution and expression of OXT receptors in nonprimate mammals (12, 13), and separate OXT-application studies in humans have indicated that there may be differential amygdala reactivity to fearful faces and fearful/threatening scenes in men (14, 15) and women (16,17). Importantly, this region plays a key role in processing so...