At the University of California, San Francisco, 17 patients who met the following criteria-hepatic tumor unresectable because of location or inadequate liver reserve, no metastases, HBsAg negative, no tumor larger than 5 cm in diameter, and no more than three tumors--were enrolled prospectively in a protocol employing preoperative chemoembolization to assess whether orthotopic liver transplantation (OLT) could cure a majority of highly selected patients with hepatocellular carcinoma (HCC). Thirteen patients had biopsy-proven HCC, 2 had the fibrolamellar variant, and 2 had radiological findings of HCC but no biopsy confirmation. Fourteen had underlying liver disease. All arteriographically apparent lesions were chemoembolized using a mixture including Gelfoam powder, doxorubicin, mitomycin-c, and cisplatin. Eight patients with poor hepatic reserve were chemoembolized when a donor organ became available, whereas 9 patients were chemoembolized and then placed on the waiting list. The only complication of chemoembolization was a gangrenous gallbladder in 1 patient. Thirteen patients underwent liver transplantation (2 patients without prior histological confirmation of carcinoma had no identifiable tumor at OLT); 3 patients developed metastases between the time of enrollment and donor organ availability and subsequently died; and 1 patient underwent a trisegmentectomy. Ten of the 11 patients with biopsy-proven HCC who underwent transplantation remain free of recurrent cancer at a median of 40 months; 1 patient died at 6 months of lymphoproliferative disease with no cancer found at autopsy. Although the role of chemoembolization is uncertain, these data show that the majority of carefully selected patients with HCC may achieve long-term survival with OLT.