During pregnancy, vascular sensitivity to A-II is reduced and it was clarified that this refractoriness to A-II is due to a change in EDRF output in pregnant rabbits. The present study aimed at elucidating whether estrogen or progesterone is responsible for the augmentation of EDRF output. 17-OH-estradiol was administered (200 micrograms/kg/day) for 7 days to 8 non-pregnant rabbits, while progesterone was similarly administered (2,000 micrograms/kg/day) to 8 other non-pregnant rabbits. Twenty-four nonpregnant rabbits were employed as the controls. Common iliac arterial rings prepared from each group were compared for the isometric response to A-II. The arterial rings with intact endothelium prepared from the progesterone-treated group were found to have a smaller pD2 value and a smaller maximum response to A-II than the estrogen-treated group. On the other hand, no differences between the progesterone group and estradiol group were observed in these values for the endothelium-denuded arterial rings. These findings indicated that the augmentation of EDRF output during pregnancy is brought about by progesterone.