Prolactin (PRL) and other lactogenic hormones feed back at the hypothalamus to inhibit PRL release. At midpregnancy, high circulating levels of placental lactogens (PL) terminate the mating-induced biphasic PRL surges in female rats. In the dark period preceding parturition, however, an ante-partum PRL surge occurs despite continuously high levels of PL. This study examined whether the lactogenic hormone negative feedback loop is altered during the ante-partum surge using two models: (i) pregnant rats given a hypothalamic implant of albumin, ovine PRL, or recombinant rat PL-I on Day 19 or 20 of pregnancy; and (ii) pregnant rats bearing a transplant of a rat choriocarcinoma cell line, Rcho-1 (PL-secreting), or HRP-1 (non-PL-secreting). Serial blood samples were taken via carotid cannula from all rats. Although lactogenic hormones placed in the hypothalamus reduced suckling-induced PRL release by 89%, hypothalamic implants of oPRL or recombinant rPL-I did not attenuate the ante-partum PRL surge. Rcho-transplanted rats also did not have a significantly reduced ante-partum PRL surge (peak PRL level, 131 ng/ml) compared with HRP-bearing rats (peak PRL level, 107 ng/ml). Northern blot analysis revealed that the Rcho-1 tumors expressed both PL-I and PL-II, while the HRP-1 tumors did not express either PL. The inability of the Rcho-1 transplants to inhibit the ante-partum PRL surge suggests that lactogenic hormone negative feedback is disrupted during the ante-partum period, possibly by the changing steroid profile associated with parturition.