Levels of progesterone, prostaglandin F2alpha (PGF2alpha) and oestradiol in the utero-ovarian venous plasma of non-pregnant and early, unilaterally pregnant guinea-pigs were compared. Progesterone levels fell from day 12 to day 15 in the non-pregnant animals, while levels of PGF2alpha and oestradiol increased during this period. In contrast, in the pregnant guinea-pigs, progesterone levels remained high up to day 15 and PGF2alpha and oestradiol levels remained low in plasma from both the pregnant and non-pregnant sides. These findings support the hypothesis that the guinea-pig conceptus secretes an anti-luteolytic factor in early pregnancy, which reduces the amount of PGF2alpha produced by the uterus and released into the uterine veins and thereby allows luteal maintenance and continued progesterone secretion. Oestradiol, in the presence of progesterone, is regarded as the physiological stimulus for normal uterine PGF2alpha synthesis and release. Consequently, the inhibition of ovarian oestradiol secretion seen in early pregnancy is probably at least part of the mechanism by which the anti-luteolytic factor produced by the conceptus reduces PGF2alpha synthesis by and release from the uterus.