Retrospective analysis of 108 patients who received indium 111-labeled murine monoclonal antibodies for imaging of cancer was performed. Most patients had operative procedures for colorectal carcinoma following completion of scintiscanning. Eleven patients had markedly elevated carcinoembryonic antigen (CEA) levels postoperatively without evidence of residual or recurrent disease. The laboratory method of measuring CEA levels was a commercially available double mouse monoclonal antibody enzyme immunoassay. It was postulated that the unexplained elevation of CEA was a reflection of the presence of human anti-mouse antibody (HAMA) induced by the administration of radiolabeled mouse antibody. A competitive assay for HAMA was undertaken by incubation of these patients' sera with a high dose of nonspecific mouse immunoglobulin prior to CEA determinations, and subsequent CEA levels were normal. The presence of HAMA was confirmed by a noncompetitive solid-phase enzyme immunoassay in 73% of tested patients who received murine monoclonal antibodies for imaging. Identification of artifactual CEA elevations is important in the treatment of cancer patients.