Prostaglandins have been implicated as regulators of uteroplacental blood flow during pregnancy. However, the investigation of the vascular effects of these humoral agents has been extremely limited. The present study has evaluated the effects of intra-arterial infusions of prostaglandin D2, E2, F2 alpha, I2, 6-keto-F1 alpha, thromboxane B2, and bolus injections of the prostaglandin precursor arachidonic acid into the uterine vasculature of late-term pregnant ewes. Prostaglandins E2, F2 alpha, 6-keto-F1 alpha, and thromboxane B2 all reduced uterine blood flow, with prostaglandins E2 and F2 alpha being much more active. Since prostaglandins E2 and F2 alpha increase uterine tone, a portion of their vascular effects appears to be due to myometrial compression. In contrast, prostaglandins D2 and I2 produced dose-related increases in uterine blood flow in pregnant animals and did not alter uterine tone or contractile activity. Arachidonic acid produced dose-related increases in uterine vascular resistance in three out of five animals and had no effect in the other two animals. The differential vascular effects produced by the individual prostaglandins and their precursor suggest that the overall effect of these compounds on the uterine vasculature will depend on the summation of the individual actions.