Portal hypertension is characterized by a pathologic increase in portal venous pressure that leads to the formation of an extensive network of portosystemic collaterals that divert a large fraction of portal blood to the systemic circulation, bypassing the liver. Experimental models have improved understanding of the pathophysiology of portal hypertension. It is now clear that an increased vascular resistance to portal blood flow is the initial factor responsible for the increase in portal pressure. This resistance is exerted along the hepatic and portal-collateral circulation and is in part modifiable by pharmacologic agents. In a latter stage, an increased portal venous blood inflow, promoted by splanchnic vasodilation, contributes to maintenance and aggravation of portal hypertension. Humoral vasodilatory agents play an important role in the splanchnic vasodilation. Several vasodilators are likely to be involved, including glucagon, prostacyclin, endotoxins, and nitric oxide. The splanchnic vasodilation is associated with a hyperkinetic systemic circulation, with reduced arterial pressure and peripheral resistance and increased cardiac output. The splanchnic circulation is probably the vascular territory in which the vasodilation is more pronounced. Therefore, splanchnic and systemic vasodilation probably share some pathophysiologic events. An expanded plasma volume is observed in all forms of portal hypertension. Expansion of plasma volume is due to renal sodium retention, which has been shown to precede the increase in cardiac output and can be prevented or reversed by sodium restriction and spironolactone. The expanded blood volume represents another mechanism that contributes to further increases in portal pressure.