A solid-phase, two-site monoclonal antibody radioimmunoassay for carcinoembryonic antigen in serum or plasma has been developed. Two monoclonal antibodies are used: 3d6, which is immobilized on polystyrene beads, reacts with high-molecular-mass CEA; the other, C4, with apparently restricted reactivity toward gastrointestinal tract and mammary carcinomas, is labeled with 125I. The assay consists of incubating 0.2 mL of serum both with 3d6-coated beads and 125I-labeled C4 at room temperature for 18 h. The CEA standard is calibrated against WHO international standard (73/601). Advantages of this assay include: (a) no heat or acid pre-treatment of samples; (b) linear response over a wider functional range, 0 to 150 micrograms/L, requiring fewer calibration points; and (c) no interference by glycosaminoglycans. Average inter- and intra-assay reproducibilities (CVs) are less than 10%; analytical recovery of CEA was 94 to 107%. CEA of less than 0.5 micrograms/L can be detected. The mean concentration of CEA in serum from healthy individuals is 0.97 (SD 1.18) micrograms/L; only 3% of the sera tested had concentrations greater than 3.0 micrograms/L. On comparing this assay with a polyclonal RIA, we found similar assay sensitivity for colorectal carcinoma but fewer false-positive results for sera from patients with benign liver and bowel diseases.