The murine antiglioma monoclonal antibody 81C6 has been shown to specifically localize in U-251 MG and D-54 MG human glioma subcutaneous and intracranial athymic mouse xenografts expressing the human gliomamesenchymal extracellular matrix glycoprotein GMEM. In paired-label studies 81C6 reached peak levels of localization in subcutaneous and intracranial xenografts in 24 to 48 hours and persisted there for an additional 5 to 7 days before declining. The percent localized 81C6 in U-251 MG subcutaneous xenografts was tumor size dependent ranging from 2% in 200-300 mg tumors to 15% in 1 gram tumors. Subcutaneous xenografts of U-251 MG were readily radioimaged from 1 up to 6 days following administration of 131-I-81C6. The specificity of 81C6 localization has also been demonstrated by tissue autoradiography, elution of radiolabeled 81C6 from tumor xenografts, and in vivo inhibition of radiolabeled 81C6 localization by unlabeled 81C6. D-54 MG intracranial xenografts were permeable to 81C6 and control immunoglobulin but specific localization occurred only with 81C6. Radiolabeled 81C6 monoclonal antibody and U-251 MG and D-54 MG human glioma xenografts provide a useful operationally tumor specific monoclonal antibody tumor localization model for the examination of monoclonal antibody pharmacokinetics, radioimaging, radioimmunotherapy and combined modality therapy in intracranial human glioma xenografts.