The effect of portal hypertension (induced by partial ligation) on the ability of the portal vein wall to produce prostacyclin (PGI2) was studied in rats over a period of 6 weeks. PGI2-like activity measured by bioassay was shown to be significantly increased in portal vein segments during established hypertension when compared to control groups. As a collateral circulation developed with consequent fall in portal venous pressure, PGI2-like activity decreased. A positive correlation between PGI2-like activity and portal pressure has been demonstrated. Parallel measurements of this activity by bioassay and radioimmunoassay to 6-keto-prostaglandin-F1 alpha showed a positive correlation (r = 0.88) and suggested that PGI2 is the inhibitory prostaglandin involved. The possible significance of these observations in relation to the hemorrhagic manifestations associated with portal hypertension in man is discussed.