To determine the possible role of prostacyclin (PGI2) as a mediator of the splanchnic hyperemia seen with portal hypertension, the portal and mesenteric hemodynamics in normal and portal hypertensive rabbits were studied before and after cyclo-oxygenase blockade. Three weeks after partial portal vein ligation, splenic pulp pressure was elevated from 4.3 +/- 0.9 to 9.8 +/- 0.8 mmHg (p less than 0.01). Mesenteric blood flow increased from 77.0 +/- 4.7 ml.min-1.100 g-1 to 99.1 +/- 5.19 ml/min-1/100 g-1. Mesenteric vascular resistance fell from 0.82 +/- 0.6 mmHg/ml-1/min-1 to 0.49 +/- 0.07 mmHg/ml-1/min-1 (p less than 0.01). These hemodynamic changes were associated with a 27.3 +/- 0.2% rise in systemic arterial levels of PGI2 (p less than 0.01) and were substantially ameliorated by cyclo-oxygenase blockade with indomethacin. The effects of indomethacin blockade were reversed by exogenous PGI2. Moreover, in normotensive rabbits, infusion of PGI2 reproduced the splanchnic hyperemia and caused a very small but significant increase in portosystemic shunting. These findings support the previously proposed concept that splanchnic hyperemia may contribute to the maintenance of chronic portal hypertension. Furthermore, they suggest that this effect may be partially mediated by splanchnic PGI2 production.