Early life stress is believed to constitute a risk factor for the development of mood disorders later in life. In the present study, we hypothesized that prenatal stress (PS) exerts long-lasting effects in female rat offspring, resulting in impaired adaptations to stress during lactation and, as such, may be a contributory factor to postpartum mood disorders. PS increased anxiety in adult virgin females compared with controls. During lactation, PS dams nursed significantly less and spent less time with pups compared with controls, whereas dams did not differ in pup retrieval or maternal aggression. HPA axis reactivity was elevated in response to a mild stressor in PS dams compared to their controls, but not in virgins, with the delta corticosterone response returning to the higher level seen in virgins. Moreover, corticotropin-releasing hormone (CRH) mRNA expression within the parvocellular region of the paraventricular nucleus (PVN) was increased in both virgins and dams exposed to PS compared with the relative controls, while the attenuation in expression in lactating controls was abolished following PS. In addition, arginine vasopressin (AVP) mRNA was increased in the parvocellular, but not magnocellular part of the PVN, in both PS-exposed virgins and lactating dams compared with their relative controls; although expression was also higher in controls during lactation compared with virgins. Thus, the present study demonstrates that exposure to PS results in long-lasting behavioural and neuroendocrine alterations in the female offspring, which are manifested during the lactation period. Furthermore, it implicates PS as a potential risk factor for the development of postpartum mood disorders, and that alterations in the HPA axis reactivity, at least partially, are involved.