The administration of [131I]B72.3 MAb for both diagnostic and therapeutic purposes is followed by the development of human anti-mouse antibodies (HAMA) in approx. 70% of patients receiving i.v. doses of MAb above 1 mg. The presence of HAMA in circulation interferes in the detection of the tumor-associated glycoprotein TAG-72 using the CA 72-4 RIA. We have reported elsewhere (Ferroni et al., 1990) that heat treatment at 90 degrees C, pH 6.5, for 15 min is capable of precipitating and/or inactivating HAMA without causing any significant loss in antigen recovery. Furthermore, the removal of the interfering activity leads to a more correct evaluation of TAG-72 serum levels in HAMA-positive serum samples and to a continued use of TAG-72 in the follow-up of patients undergoing MAb-based clinical protocols.