Changes in intestinal mucosal microvasculature as a cause of lower gastrointestinal hemorrhage in patients with portal hypertension have been well documented clinically, but the analogous histomorphological changes have not been well characterized. The goal of this study was to evaluate qualitative and quantitative changes in colonic mucosal vessels in patients with cirrhosis or clinically evident portal hypertension and to correlate these changes with endoscopic and clinical findings. Colon biopsy or resection specimen slides from 46 patients with biopsy-proven cirrhosis (44 patients) or noncirrhotic portal hypertension (two patients) were reviewed. Immunoperoxidase stain for CD34 antigen was used to facilitate visualization of mucosal vessels, and vessel diameter was measured with a micrometer. Patients with inflammatory bowel disease were excluded. Twenty-four normal colon biopsy specimens served as controls. Mucosal vessels were divided into superficial, intermediate, and deep layers. As a group, the cirrhotic patients had a significantly higher mean diameter of vessels in all three layers. Qualitatively, increased numbers of small vessels and prominent branching were noted, especially in the superficial and intermediate layers. Tortuous, thick-walled vessels, suggesting arterialization of venules, were present in some cases. Eleven patients had endoscopic findings suggestive of vascular abnormalities, including erythematous mucosal patches, red macules, and telangiectasias. Eighteen had esophageal varices, and five had portal gastropathy. Nineteen patients had gastrointestinal (GI) bleeding, localized to the lower GI tract in 11. These qualitative and quantitative findings suggest that colonic mucosal vascular lesions are common in portal hypertension and may represent a potential source of clinically significant lower GI hemorrhage in these patients.