Although it has often been speculated that prior reproductive experience improves subsequent maternal care, few studies have examined specific changes in behavior during a 1st versus 2nd lactation. During lactation, mothers display heightened aggression toward male intruders, purportedly to protect vulnerable young. In the current study, maternal aggression was examined in primiparous and age-matched multiparous females on postpartum days 5 (PPD5) and PPD15. Expression of oxytocin, oxytocin receptor, arginine vasopressin, arginine vasopressin V1a receptors, and corticotrophin-releasing hormone mRNA was measured following aggression testing at both time points using real-time quantitative PCR in brain regions previously implicated in the regulation of maternal aggression. Multiparity significantly enhanced maternal aggression on PPD5 but not on PPD15. In addition, this increased aggression was associated with region- and gene-specific changes in mRNA expression. These findings indicate that reproductive experience enhances maternal aggression, an effect that may be mediated by region-specific alterations in neuropeptidergic activity. The adaptations observed in multiparous females provide an innate model for the study of neuroplasticity in the regulation of aggression.