Monoclonal antibodies directed at tumor-associated antigens may be useful adjuncts for the management of patients with colorectal cancer. The murine monoclonal antibody, B72.3, binds Tag-72, a cell-surface antigen, which is expressed by colorectal carcinoma cells. We investigated the benefit of indium-111-labeled B72.3, 111In-CYT-103, in localizing the presence and extent of disease in patients with suspected or biopsy-proven primary colorectal cancer and in patients with apparently localized recurrent colorectal adenocarcinoma. Twenty patients were enrolled in this study. Each patient received 1 mg of B72.3 labeled with 4 to 5 mCi of 111In. Patients then underwent planar and single-photon emission computed tomographic imaging 2 to 5 days after infusion. Fifteen patients underwent surgery 1 to 14 days after scanning. There were 11 true positives, 1 false positive, 2 true negatives, and 1 false negative. The 111In-CYT-103 scan correctly identified the presence or absence of tumor in the 15 patients in whom biopsies were obtained, for an accuracy rate of 87%. Overall, 111In-CYT-103 supplied clinically useful information regarding the extent of disease that was not previously reported by standard techniques in 33% (5 of 15) of patients who underwent surgical exploration. We conclude that 111In-CYT-103 is a promising imaging agent for patients with potentially resectable recurrences and for those patients with a presumed isolated primary tumor requiring preoperative staging.