Acute and chronic effect of verapamil on estimated hepatic blood flow were investigated in 12 patients with HBsAg-positive cirrhosis and portal hypertension. Acute administration of verapamil results in a significant increase (8%) in estimated hepatic blood flow (p less than 0.05). However, after chronic continued administration of verapamil, the mean value of estimated hepatic blood flow remains unchanged vis-a-vis basal values. Acute and chronic use of verapamil significantly reduced the hepatic venous pressure gradient for about an average of 20% at 1 hr after drug administration (p less than 0.05) and 18% 2 weeks later (p less than 0.05). This drop was associated with a significant reduction in hepatic vascular resistance by 39% at 1 hr later and by 37% 2 weeks later. Furthermore, the drop in hepatic vascular resistance was independent of any verapamil-induced changes in systemic hemodynamics. Verapamil significantly increased the indocyanine green plasma clearance and extraction ratio after acute or chronic use of the drug. We conclude that in patients with HBsAg-positive cirrhosis, the mechanism of verapamil in reducing the hepatic venous pressure gradient is predominantly by inducing a drop in hepatic portal vascular resistance.