Five groups (n = 4) of congenitally athymic female nude mice bearing subcutaneous implants of CX-1 and/or SW-1116 tumor in the hind limbs received iodine-125 radio-labeled monoclonal antibodies (MoAbs) B72.3 (two groups), 17-1A (two groups), and cocktail (one group) (iodogen method, 50 microCi/10 micrograms/mouse). Daily probe counts were made in duplicate with a hand-held detector over each tumor site and the front leg (background) for 21 days. Animals were sacrificed and appropriate well counts were obtained. All the single MoAb preparations localized well in both tumor cell lines. Uptake of monoclonal antibody 17-1A was similar in the two tumor cell lines, with counts initially high and slowly decreasing over the 21-day period. Tumor/background ratios continued to increase over time, indicating that both tumor lines have similar antigenic expression for the monoclonal antibody 17-1A. This was not the case for monoclonal antibody B72.3, which showed a preferential uptake by the CX-1 tumor, with higher initial counts and prolonged binding of the antibody, giving rise to higher tumor/background ratios. The mixture of monoclonal antibodies B72.3 and 17-1A markedly improved the uptake by the CX-1 tumor cell line but not that by the SW-1116 cell line, where the effect was negative when compared to the uptake of the single MoAb preparations. The use of a monoclonal antibody mixture can enhance targeting of some tumor sites. Due to the heterogeneity of tumor cell lines, even within the same animal, different mixtures of monoclonal antibodies are needed to increase the targeting of tumor.