Recent clinical observations led to the use of external radiation to increase tumor targeting by radiolabelled 131-I antiferritin. Examination of increased uptake of 131-I labelled antiferritin following external radiation was carried out in syngeneic implanted hepatomas (H4IIE, 3924A, 7800, and 7777). Exposure to 10 Gy increased the tumor: liver uptake ratio from 1.55 to 1.86 for H4IIE; from 1.56 to 2.0 for 7800; from 1.34 to 1.97 for 7777; and from 1.05 to 1.19 for 3924A. The pattern of uptake varied among the different tumor types, reflecting their inherent differences in vascularity, tumor permeability, antigen density and growth rate, all of which influence antibody targeting of the tumors. When tumor and liver were irradiated, the tumor showed increased differential uptake of labelled antibody compared to normal liver. 51-Cr labelled erythrocytes were used to study the relative vascularity and blood pooling in H4IIE hepatoma and normal tissue. External radiation to the tumor did not increase the uptake of 51-Cr labelled erythrocytes in any site. These studies provide an insight into the role of external radiation as a modality that increases radiolabelled antibody targeting in hepatoma.