Twenty-one patients with biopsy-proven hepatocellular carcinoma were treated with oral or intravenous 5-Fluorouracil according to a randomized treatment schedule. Twenty-one patients were evaluable for response and toxicity. The two groups were comparable in distribution of pretreatment characteristics. There were no objective responses in either group. This is the largest reported group of patients with hepatocellular carcinoma treated with 5-Fluorouracil. Toxicity occurred in 46% of patients treated, but was tolerable. In contrast to previous reports, we have found that weekly 5-Fluorouracil given orally or intravenously is not of significant value in the treatment of hepatocellular carcinoma.