Our purpose was to determine, in a prospective study, the causes of gastrointestinal hemorrhage in patients with hepatocellular carcinoma, and the relationship of portal vein invasion with variceal hemorrhage in these patients. During an 11-month period, 55 patients presented with hepatocellular carcinoma presented with signs and/or symptoms of upper gastrointestinal hemorrhage. Forty-seven percent had bleeding from varices, whereas the majority, 53%, had a nonvariceal bleeding source. Among those with nonvariceal bleeding, duodenal ulceration was the commonest cause. Direct tumor invasion into the gastrointestinal tract was found in three patients. Tumor invasion of the portal venous system was detected by ultrasound examination in 76% of the variceal bleeders, compared to only 45% of the nonvariceal bleeders. Despite the very high frequency of cirrhosis among patients with hepatocellular carcinoma, the source of bleeding was variceal in less than half of the patients. Portal vein invasion is a risk factor for subsequent variceal bleed.