The effects of external beam radiation on tumor uptake of radiolabeled monoclonal antibody were investigated. Nude mice bearing carcinoembryonic antigen (CEA)-producing subcutaneous human tumor xenografts (LS174T) were irradiated (60Co) with a single fraction of 0, 2 or 20 Gy, 6 or 11 days after tumor inoculation. An Indium-111 labeled anti-CEA monoclonal antibody (T84.66) was injected 1-2 hrs after irradiation. Biodistribution studies performed at 48 hrs showed a statistically significant (p less than 0.01) inverse correlation between tumor mass and tumor antibody uptake. Tumor age was also a significant factor with 11 day old tumors having significantly less uptake (p less than 0.0001) compared to 6 day old tumors for a given mass. Radiation increased tumor antibody uptake only in those tumors where growth inhibition also occurred. Multiple regression analysis showed that this inverse correlation between tumor mass and antibody uptake was the same for irradiated and nonirradiated tumors. We conclude that, in this model system, radiation does not act independently to enhance tumor antibody deposition. Radiation's primary effect is to reduce tumor mass, with mass reduction then resulting in an increase in antibody uptake. The clinical implications of this study are discussed.