Because prolonged estrogen therapy can initiate hepatic adenomas, and estrogen receptors (ER) are found in 33% of hepatocellular carcinomas, a Phase II study of antiestrogen therapy was initiated in patients with hepatocellular carcinoma. Tamoxifen (20 mg twice a day) was administered to 33 patients who had biopsy proven and measurable hepatocellular carcinoma and who had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. No patient had a complete or partial antitumor response; eight patients had stable disease ranging from 5 to 13 months. The median survival time for all patients was 6 months from the initiation of tamoxifen therapy. Four patients have continuing long-term survival of 18+, 22+, and 39+ months.