Human anti-(murine Ig) antibody (HAMA) responses were monitored in 32 patients with unresectable hepatocellular carcinoma (HCC) undergoing radioimmunotherapy using 131I-labeled anti-HCC monoclonal antibody (Hepama-1 mAb) intrahepatic arterial infusion. Dosages of Hepama-1 mAb ranged from 5 mg to 20 mg and the mAb was radiolabeled with 0.74-4.00 GBq (20-108 mCi) 131I (4-6 mCi/mg). T lymphocyte subsets were examined before and after radioimmunotherapy in 24 patients. In this series, 34.4% (11/32) of patients developed HAMA within 2-4 weeks after the infusion. All patients with a negative HAMA response (n = 14), had CD4+ T lymphocyte subsets (T helper/inducer) much lower than those of the HAMA-positive (n = 10) patients and the control group (n = 40) (P < 0.01) prior to infusion. The sequential resection and survival rates in the HAMA-negative group were also lower than that of the HAMA-positive group. Thus, the determination of T lymphocyte subsets might help to predict the HAMA response in HCC patients during radioimmunotherapy.