The effect of RU486, a synthetic progesterone receptor antagonist, on basal uterine prostaglandin (PG) release and release in response to oxytocin injection has been investigated in late-pregnant sheep (days 135-140 of gestation). Fifteen hours after i.m. injection of RU486 (50 mg; n = 5) or vehicle alone (n = 4), bolus injections of oxytocin (50, 500 and 5000 mU) were administered via a uterine artery ipsilateral to the pregnant uterine horn at 2-hourly intervals. Utero-ovarian vein concentrations of 13,14-dihydro-15-keto PGF(2α) (PGFM) and PGE2 were determined before and during oxytocin stimulation. Basal concentrations of both PGFM and PGE2 were significantly (P < 0.001) increased in ewes 15 h after RU486 administration compared with ewes receiving vehicle alone. Concentrations of PGFM, but not PGE2, increased significantly (P < 0.001) following injection of each dose of oxytocin in both treated and untreated animals. The response to oxytocin, measured both as the area under the curve and as the peak height of PGFM release, was significantly (P < 0.05) greater in RU486-treated ewes. There was no significant effect of oxytocin on the area or peak height of PGE2 response in either RU486-treated or control animals. These results demonstrate that treatment of late-pregnant ewes with RU486 results in an increase in basal uterine PGFM and PGE2 as well as oxytocin-stimulated PGFM release.