Prostaglandin (PG) I2 and 6-keto-PGE1 were infused into the aortic arch, femoral vein, renal artery and portal vein in anesthetized dogs over a dose range to produce a stable decrease in systemic blood pressure after 7 min of infusion. Mesenteric artery blood flow was measured continuously with a non-cannulating electromagnetic flow probe. Parallel log dose-response relationship were seen for decreases in blood pressure and increases in mesenteric blood flow with both prostaglandins when infused into the aortic arch. The dose responses for intra-aortic and intravenous infusion of PGI2 were not different but were shifted to the right with intrarenal and intraportal infusions. With 6-keto-PGE1 the dose responses after intravenous, intrarenal and intraportal infusions were all shifted to the right. By comparing doses which reduced blood pressure by 10 mm Hg, the extraction of the PGs by the lungs, kidney and liver was calculated PGI2 had no significant pulmonary extraction. 31% renal and 75% hepatic extraction. In contrast, 6-keto-PGE1 had extractions of 40, 66 and 51% for pulmonary, renal, and hepatic vascular beds, respectively. We conclude that 6-keto-PGE1 is reasonably well extracted by the lungs, kidney, and liver.