The role of prostaglandins in mediating the increased endometrial vascular permeability which results from the application of an artificial stimulus to the uterus of the rat sensitized for the decidual cell reaction was investigated. Immature rats were pretreated so that at the time of application of the artificial stimulus, the unilateral injection into the uterine lumen of 50 µl phosphate buffered saline containing gelatin, their uteri were sensitized for the decidual cell reaction. Endometrial vascular permeability was quantified with [¹²⁵I]-labelled bovine serum albumin ([¹²⁵I]-BSA); the ratio of the concentrations of radioactivity in the injected to noninjected uterine horns 15 min after an i.v. injection of [¹²⁵I]-BSA was used as an index of the effect of the stimulus on endometrial vascular permeability. Indomethacin, an inhibitor of prostaglandin biosynthesis, significantly reduced the endometrial vascular permeability indices of rats killed 4 or 8 h after the intraluminal treatment. Compared to the noninjected horn, the concentrations of prostaglandins of both the E and F series were markedly elevated within 15 min in the injected uterine horn and remained elevated for at least 2 h. When injected into the uterine lumen of rats treated with indomethacin to inhibit endogenous prostaglandin production, prostaglandin E₂, but not prostaglandin F_2α, increased the endometrial vascular permeability index. When given together into the uterine lumen, prostaglandin F_2α inhibited the stimulatory effect of prostaglandin E₂ on the endometrial vascular permeability index. These results suggest that prostaglandins, probably of the E series, may be the mediators of the increased endometrial vascular permeability which results from the application of an artificial stimulus to the sensitized rat uterus.