Jugular venous concentrations of oxytocin and progesterone changed in parallel during the oestrous cycle in the ewe, falling at luteal regression and rising with formation of the new corpus luteum. These fluctuations in the circulating concentration of oxytocin were not caused by changes in its metabolic clearance rate. On Days 6-9 of the cycle circulating oxytocin concentrations exhibited a diurnal rhythm, peaking at 09:00 h; this rhythm was absent on Days 11-14. Although there was no evidence for increased production of oxytocin at or preceding luteal regression in samples taken daily, more frequent sampling revealed that two thirds of detected surges of uterine secretion of prostaglandin (PG) F-2 alpha were accompanied by raised levels of oxytocin. This oxytocin was not of pituitary origin. Luteal regression induced with cloprostenol on Day 8 after oestrus caused a decrease in circulating progesterone level followed after 24 h by a fall in oxytocin. Measurements of oxytocin in the ovary and other organs before and after treatment with cloprostenol identified the corpora lutea as a major potential source of oxytocin, and suggested that 98% of luteal oxytocin was available for secretion in response to prostaglandin stimulation. The data are consistent with a role for ovarian secretion of oxytocin in response to uterine release of PGF-2 alpha in the control of luteal regression.