Abstract Central arginine vasopressin receptor 1A (AVPR1A) modulates a wide range of behaviors, including stress management and territorial aggression, as well as social bonding and recognition. Inter- and intra-species variations in AVPR1A brain expression patterns and downstream differential behavioural phenotypes have been attributed to differences in the 5′ non-coding region upstream of the AVPR1A gene including polymorphic elements within this regulatory area. Gene association studies have suggested a link between AVPR1A polymorphisms and autism and AVPR1A has emerged as a potential pharmacological target for treatment of social cognitive impairments and mood and anxiety disorders. To further investigate the genetic mechanism giving rise to species differences in AVPR1A expression patterns and associated social behaviors, and to create a preclinical mouse model useful for screening drugs targeting AVPR1A, we engineered and extensively characterized BAC transgenic mice harboring the entire human AVPR1A locus with the surrounding regulatory elements. Compared to wildtype animals, the humanized mice (hAVPR1A) displayed a more widely distributed AVPR1A binding pattern, with overlap with primate expression. Furthermore, hAVPR1A mice displayed increased reciprocal social interactions compared to wildtype animals, but no differences in social approach and preference for social novelty were observed. Aspects of learning and memory, specifically novel object recognition and spatial relocation recognition, were unaffected. The biological alterations in hAVPR1A mice resulted in the rescue of prepulse inhibition impairments observed in knockout mice, indicating conserved functionality. Although further behavioural paradigms and additional cohorts need to be examined in hAVPR1A mice, the results demonstrate that species-specific variations in the genomic content of regulatory regions surrounding the AVPR1A locus are likely responsible for differential receptor protein expression patterns across species and contribute to species-specific behavioral variation. The hAVPR1A mouse is a potential preclinical model for further understanding the regulation of receptor gene expression and the impact of variation in receptor expression on behaviors, and should be useful for screening drugs targeting human AVPR1A.