Brain arginine vasopressin (AVP) not only regulates male social behavior and emotionality, but also promotes maternal behavior, as has been shown in rats. In our CD1 mice breed for high (HAB) or low (LAB) anxiety-related behavior, LAB mice have markedly less AVP mRNA expression in the hypothalamic paraventricular nucleus compared with HAB mice. Together these findings suggest that HAB and LAB mice represent a good model to assess the role of AVP in mouse maternal behavior. Therefore, we studied maternal care of HAB and LAB mouse dams and investigated the impact of maternal care on the offspring's anxiety in a cross-fostering paradigm. In comparison with HAB dams, LABs displayed less maternal care. Daily acute intracerebroventricular infusions of AVP in early lactation increased maternal care of LAB dams and acted anxiogenically. Cross-fostering on postnatal day 5 did not alter separation-induced high and low ultrasonic vocalization calling frequency, a measure of inborn anxiety, in HAB and LAB offspring, respectively. However, adult cross-fostered HAB mice displayed a trend towards decreased anxiety on the elevated plus-maze, which was still significantly higher compared with LAB mice. The low levels of depressive-like behavior, stress-reactivity, and hypothalamic AVP mRNA expression in adult LAB offspring were found to be independent of cross-fostering. In conclusion, the HAB/LAB differences in maternal care and anxiety are robust and strongly depend on differences in the AVP system. The seemingly rigid genetic predisposition to hyperanxiety can only be moderately attenuated by the received nurturing.