To assess the importance of monoclonal antibody route of administration, we compared the selective (intraportal) and systemic injection of specific radiolabeled monoclonal antibody, using a murine model of hepatic metastases from a human colorectal carcinoma. Tumor uptake was studied over time after injection of 0.1, 1.0 or 2.0 micrograms of a specific antibody (HT29-15) or an isotype-matched control (BL-3). Significantly higher tumor uptake and tumor/liver or tumor/blood uptake ratios were seen in animals receiving intraportal injection for all tested doses. Intraportal injection of specific monoclonal antibody resulted in significant improvement in metastases uptake; these findings could be applied to the diagnosis and treatment of hepatic metastases from colorectal cancer using radiolabeled monoclonal antibodies.