In an attempt to obtain complete tumor necrosis in large hepatocellular carcinoma (HCC) lesions, the authors studied the clinical and histologic findings of a new combination therapy, percutaneous ethanol injection (PEI) with transcatheter arterial embolization (TAE) (pretreatment with TAE and subsequent PEI) in 15 patients with a single, large (3.0-9.0 cm in diameter), encapsulated lesion of HCC. Two weeks after TAE, PEI was performed under ultrasound guidance. A total of four to 11 injections were administered at a rate of one injection twice a week. During the follow-up period (range, 7-23 months), all lesions were reduced in size and no evidence of HCC was present at contrast material-enhanced computed tomography or angiography in nine of 11 patients who did not subsequently undergo surgery. Six patients had a follow-up of 1 year or more, for a 1-year survival rate of 100%. Four patients subsequently underwent surgical resection; complete necrosis of the tumor was observed in all four. The authors conclude that a combination of PEI and TAE is an appropriate treatment for patients with large, encapsulated HCC lesions who are poor surgical risks.