Murine monoclonal antibody RS5-4H6 is an IgG1, which was raised against a crude membrane preparation of Calu-3, a human adenocarcinoma of the lung cell line. MAb RS5-4H6 reacts with the majority (14 of 15) of surgical specimens of non-small cell carcinomas of the lung by immunoperoxidase staining. Reactivity with this antibody was not limited to tumors of the lung but rather exhibited pancarcinoma reactivity, staining 87% of tumors from all organs tested. In this study we examined the potential of radiolabeled RS5-4H6 to target Calu-3 xenografts in nude mice. The monoclonal antibody was found to localize preferentially to the heterotransplanted tumors, with 6.6% of the injected dose/g accreting in the tumor at 7 days, a 3-fold higher level than an anti-carcinoembryonic antigen monoclonal antibody which was used as a negative control.