The naturally occurring social conflict situation to be confronted with an aggressive dominant conspecific was used to study the effects of emotional stress on the release of oxytocin (OXT) and arginine vasopressin (AVP) within the mediolateral septum of the rat brain. Male rats were chronically implanted with a microdialysis probe into this brain area. Local release patterns of both, OXT and AVP were monitored in response to a 30 min social defeat. Social defeat caused a significant increase in the release of OXT (to 254%+/-43%, P<0.01). In contrast, the release of AVP was not affected. In a preliminary experiment, to assess the physiological significance of stress-induced intraseptal OXT release, a separate group of animals received the OXT receptor antagonist des-Gly-NH(2)d(CH(2))(5)[Tyr(Me)(2)Thr(4)]OVT into the mediolateral septum via inverse microdialysis prior to and during the social defeat procedure. However, no difference could be observed in submissive freezing (passive coping) or in exploratory behavior (active coping) when compared to vehicle-treated animals, neither acutely nor 24 h after antagonist administration. Taken together, our results demonstrate that emotional stress activates the septal oxytocinergic, but not vasopressinergic, system. The physiological significance of intraseptally released OXT remains unclear and has to be elucidated in future studies.