Radiolabeled B72.3 (anti-TAG-72) has been shown to selectively localize metastatic lesions in 70%-80% of the cases. Serum samples from 27 colorectal carcinoma patients who received iodine-131-(131I) B72.3 by i.v. administration were analyzed. Circulating immunoreactive antibody followed a biphasic clearance pattern. High-performance liquid chromatography (HPLC) and SDS-polyacrylamide gel electrophoresis demonstrated that 131I-B72.3 retained its integrity in the patients' sera. HPLC analysis also demonstrated the presence of immune complexes in the sera of 12 patients; this correlated with elevated levels of circulating TAG-72. Several different HAMA response patterns were detected in the 25 patients' sera that were analyzed; some patients developed HAMA as early as 5-7 days post-MAb injection. Higher doses of administered MAb B72.3 correlated with the development of HAMA (p = 0.007). The presence of elevated levels of TAG-72 in the patients' pre-inoculum serum was shown to correlate with the detection of lesions by gamma scanning. Serum TAG-72 may serve as a criteria for patient selection for immunodiagnostic or immunotherapeutic procedures using MAb B72.3.