Portal hemodynamics and transhepatic portal venographic findings were studied before and after prophylactic sclerotherapy (mean duration = 40 +/- 14 days) in 16 patients with high-risk esophageal varices. Portal pressure, evaluated by the portal venous pressure gradient, increased by a mean of 21% in eight patients (50%) and decreased by a mean of 20% in eight patients (50%) with no statistically significant change overall. The two groups were further analyzed separately to identify the mechanism of the change in portal pressure. Intrahepatic vascular resistance did not change significantly in either group. However, the prevalence of extravariceal portosystemic shunts was greater in patients with decreased portal pressure than in those with increased portal pressure (88% vs. 25%, p < 0.05). Further, the enlargement of extravariceal portosystemic shunts was more marked in patients with decreased portal pressure than in those with increased portal pressure (88% vs. 0%, p < 0.01). In addition, liver function, assessed by intrinsic clearance, was not modified in the two groups. We conclude that prophylactic sclerotherapy increases or decreases portal pressure without modifying liver function. Although the mechanism of these portal pressure changes is not clear, intrahepatic vascular resistance does not play an important role and the presence of extravariceal portosystemic shunts may prevent further increases in portal pressure.