The objective of the present study was to determine whether or not the neuropeptide, oxytocin, can move by counter current transfer from venous blood of the perihypophyseal cavernous sinus into arterial blood of the carotid rete supplying the brain and hypophysis, and also whether this exchange depends on the day of the estrous cycle. Isolated heads of gilts (n = 37), on different days of the estrous cycle, were supplied with autologous, oxygenated and heated blood at a stable blood flow and pressure through the right carotid artery for 30 min. 125I-Oxytocin (125I-OT) was infused into both cavernous sinuses through the angularis oculi veins for 5 min. After 125I-OT infusion, radiolabeled oxytocin was found in arterial blood taken from the carotid rete in all 7 gilts on Days 1-3, and in 7 of 9 gilts on Days 12-13 of the estrous cycle. In general, the level of radioactivity in arterial blood during Days 12-13 was significantly lower (p < 0.002) than during Days 1-3 of the estrous cycle. No 125I-OT was found in arterial blood from Days 4 through 11 (n = 10) or from Day 14 to the beginning of ovulation (n = 11). These results provide evidence for the counter current transfer of oxytocin from hypophyseal and brain venous effluent (cavernous sinus) to arterial blood supplying the hypophysis and brain, during the ovulation period and the late luteal phase of the estrous cycle. The meaning of this process is not as yet known and needs further study.