It has previously been observed in animal studies that, at equivalent doses, radioimmunotherapy (RIT) is 2.5 times more effective than multiple fractions of external beam radiation therapy (EBRT) in inhibiting tumour growth. In this study, we compared the use of RIT and EBRT in patients with hepatocellular carcinoma (HCC), treated during the past 10 years. Of 67 patients without extrahepatic involvement, 32 were treated with hepatic artery ligation combined with RIT (the RIT group) while 35 were treated with a combination of hepatic arterial chemo-embolisation and EBRT (the EBRT group). The patients in the RIT group received (131)I-Hepama-1 monoclonal antibody, which was infused through the hepatic artery catheter. The patients in the EBRT group received transcatheter arterial chemo-embolisation and limited-field EBRT using a linear accelerator. Parameters observed include tumour response, alpha-fetoprotein (AFP) level in serum, human anti-murine antibody (HAMA) assay, T lymphocyte subsets, survival rates, routine parameters, sequential resection rates and histopathological status of the resection specimens. The sequential resection rates were 53% (17/32) and 23% (8/35), and tumour response rates were 72% (23/32) and 86% (30/35) in the RIT and EBRT groups, respectively. The main side-effects in the RIT group were mild allergic reactions. The most common toxicity in the EBRT group was an increase in liver enzymes. The liver tissue in the target volume was injured by EBRT. The injured liver tissue revealed a low-attenuation area adjacent to the hepatic tumour within the target volume on follow-up computed tomography studies after EBRT. On pathological evaluation, the low-attenuation area revealed hyperaemia, distended hepatic sinusoids packed with erythrocytes and hepatic cell loss. The sequential resection specimens from both the RIT and the EBRT group showed residual cancer tissue located at the edge of the mass. The residual cancer cells presented as giant cells under microscopy. T lymphocyte subsets observed prior to treatment did not significantly change after RIT, but were significantly disturbed by EBRT. HAMA formation was the major reason for discontinuing RIT, the incidence being as high as 34% (11/32). Intrahepatic and pulmonary metastases occurred more frequently in the EBRT group (63%) than in the RIT group (22%). The 1-, 2-, 3- and 4-year survival rates were 50%, 41%, 34% and 31% in the RIT group, and 77%, 39%, 11% and 7% in the EBRT group, respectively. It is interesting that the serum AFP level showed a transient increase, the mechanism and importance of which are not known, but are discussed. Both RIT and EBRT are useful treatment modalities for unresectable HCC, serving to prolong survival. However, RIT is much less toxic than EBRT, the side-effects of which include radiation injury to the liver and disturbance of T lymphocyte subsets.