We studied 18 consecutive patients with advanced colorectal cancer where primary tumors were preselected for high expression of TAG-72 antigen and who underwent a phase I radioimmunotherapy trial with an intravenously administered monoclonal antibody CC49, 20 mg, labeled with I-131 in amounts varying from 15 mCi/m2 to 75 mCi/m2. Whole-body images and SPECT of the abdomen obtained 1 week after infusion were compared with pretreatment CT scans. A total of 66 lesions were evaluated. SPECT revealed 2/66 lesions (3%) that were not detected by CT; 4/66 were only detected by CT: lungs (1.8 cm and < 1 cm), axilla (1.5 cm), adrenal (2.5 cm). Thus, based on immunohistopathological testing in paraffin-embedded tissue blocks of primary tumors stained for TAG-72 antigen, we have selected a subset of patients (about 70% of referrals) with colorectal cancer for whom I-131-CC49 was shown to target to 62/64 CT positive lesions (97%) and 62/66 (94%) of all known positive lesions. We conclude that in patients with significant TAG-72 tumor expression there is excellent targeting of I-131-CC49 in therapeutic doses to colorectal cancer with respect to lesions detected with CT scanning. It should be noted that this study was not designed as a comparison of the sensitivity of CT versus I-131-CC49 SPECT/planar imaging. Instead, the observed results are consistent with a biological hypothesis that in general, the primary tumor histology vis-à-vis TAG-72 expression reflects the TAG-72 expression of the metastatic sites.