Corticotropin-releasing factor (CRF) acts as a neurotransmitter in brain to promote behavioral responses such as flight and immobility, which have adaptive value in the context of exposure to environmental stressors. CRF also suppresses behavioral repertoires such as mating, which are incompatible with such threat-related coping responses. In this study, we employed transgenic (Tg) mice which overexpress CRF in brain and exhibit a constitutive and persistent phenotype of emotionality in order to determine the consequences of long-term CRF excess on indices of reproductive success, male sexual performance and female sexual receptivity. Sexual performance of CRF Tg males was relatively intact, whereas female receptivity was masked in CRF Tg mice by active rejection of sexually experienced male counterparts. This impairment in social interaction was only partially normalized by the serotonin antagonist, methysergide, which enhanced olfactory exploration of the still non-receptive CRF Tg females. Moreover, the anxiogenic-like character of CRF Tg mice is likely to be centrally mediated, since attenuation of hypercorticosteronemia by adrenalectomy did not alter either impaired sexual receptivity or fear-like behavior in an animal model of anxiety. Thus, overexpression of CRF in the brain results in a variety of adverse consequences including diminished social interactions.