The serum levels of prostacyclin in portal venous blood samples from patients with portal hypertension were measured by radioimmunoassay to assess the role of prostacyclin in this clinical entity. Portal venous prostacyclin activity exceeded peripheral venous activity 2-3 fold in both cirrhotics and non-cirrhotics. The size of esophageal varices showed an inverse relation to the concentration of portal venous prostacyclin in the cirrhotics. There was no significant difference between the portal vein pressure and the size of varices, and the portal vein pressure did not correlate with the concentration of 6 keto-PGF1 alpha. Thus, serum levels of portal venous prostacyclin may depend on the development of collateral circulation in cirrhotics and increased splanchnic blood flow probably accelerates the washout effect.