Arterial levels of 13,14-dihydro-15-keto-PGE2 (PGE2-M), a stable metabolite of prostaglandin E2 (PGE2) were compared between unanesthetized pregnant (n = 12) and nonpregnant (n = 8) rabbits with the aim of elucidating the role PGE2 in the development of physiological hypotension associated with pregnancy. On the 20th and 22nd days of the 30 day gestation period the mean arterial concentrations of PGE2-M were about 10-times higher (p less than 0.05) and largely variable as compared to that of nonpregnant rabbits. Mean arterial pressure was not lower on either the 20th (69 +/- 4 mmHg, mean +/- SD) or the 22nd (70 +/- 3 mmHg) days of gestation (dg) than in nonpregnant rabbits (69 +/- 4 and 73 +/- 6 mmHg, respectively). On the 23rd dg hypotension was invariably present (61 +/- 5 mmHg vs 72 +/- 4 in nonpregnants, p less than 0.001), but arterial levels of PGE2-M (31.0 +/- 31.6 ng/ml) did not overcome those measured on earlier, normotensive days of gestation. Hypotension was also evident in a subgroup of pregnant rabbits (n = 4) with low PGE2-M concentrations in the nonpregnant range (3.2 +/- 1.5 ng/ml vs 1.9 +/- 1.2 in nonpregnant rabbits, ns). Since the arterial level of PGE2-M proved to correlate (p less than 0.001) with both the uteroplacental venous and renal venous PGE2 concentrations, we suggest that a key role of uteroplacental and renal PGE2 played in the development of gestational hypotension is not probable in rabbits.