Intestinal secretion and intercellular space dilatation can be induced in animal models by acute elevation of intravascular volume or portal pressure. We examined whether patients with increased portal venous pressure might represent a clinical counterpart to these animal models. Portal venous pressure, determined by hepatic wedge pressure measurement, was elevated to 10–55 mmHg (mean 29 mmHg) in 8 patients with chronic liver disease without diarrhea. Intestinal transport studies utilizing a steady-state perfusion technique revealed normal absorption of a plasmalike electrolyte solution. A solution designed to unmask intestinal secretion demonstrated no difference from control subjects in the movement of water, electrolytes, or protein into the intestinal lumen. There was no correlation of absorption or secretion with hepatic wedge pressure. Jejunal biopsy revealed a significant increase in dilatation of intercellular spaces in patients compared to controls; this increase was not correlated with hepatic wedge pressure, but was significantly inversely correlated to plasma renin and aldosterone concentration. We conclude that patients with chronic liver disease and portal hypertension absorb water and electrolytes normally, but have mild morphologic alterations in the intestinal mucosa, possibly related to intravascular volume status.