Dramatic cardiovascular alterations occur during normal ovine pregnancy which may be associated with increased prostaglandin production, especially of uteroplacental origin. To study this, we examined (Exp 1) the relationships between cardiovascular alterations, e.g., the rise in uterine blood flow and fall in systemic vascular resistance, and arterial concentrations of prostaglandin metabolites (PGEM, PGFM and 6-keto-PGF(1α)) in nonpregnant (n = 4) and pregnant (n = 8) ewes. To determine the potential uteroplacental contribution of these eicosanoids in pregnancy, we also studied (Exp 2) the relationship between uterine blood flow and the uterine venous-arterial concentration differences of PGE2, PGF(2α), PGFM, 6-keto-PGF(1α), and TxB2 in twelve additional late pregnant ewes. Pregnancy was associated with a 37-fold increase in uterine blood flow and a proportionate (27-fold) fall in uterine vascular resistance (p < 0.01). Arterial concentrations of PGEM were similar in nonpregnant and pregnant ewes (316 ± 19 and 245 ± 38 pg/ml), while levels of PGFM and PGI2 metabolite 6-keto-PGF(1α) were elevated 23-fold (31 ± 14 to 708 ± 244 pg/ml) and 14-fold (12 ± 4 to 163 ± 78 pg/ml), respectively (p < 0.01). Higher uterine venous versus uterine arterial concentrations were observed for PGE2 (397 ± 36 and 293 ± 22 pg/ml) and 6-keto-PGF(1α) (269 ± 32 and 204 ± 32 pg/ml), p < 0.05, but not PGF(2α) or TxB2. Although PGFM concentrations appeared to be greater in uterine venous (1197 ± 225 pg/ml) as compared to uterine arterial (738 ± 150 pg/ml) plasma, this did not reach significance (0.05 < p < 0.1). In normal ovine pregnancy arterial levels of PGI2 are increased, which may in part reflect increased uteroplacental production. Moreover the gravid ovine uterus also appears to produce PGE2 and metabolize PGF(2α).