It has been shown that a TAA termed rat CEA had the tissue distribution and physico-chemical properties similar to those of human CEA. In addition, it has been demonstrated that these two antigens shared antigenic determinants. These findings supported our contention that rat CEA and human CEA are analogous moieties. The production of CEA-specific autoantibodies and the induction of resistance to CEA-positive rat tumors after immunization of rats with extracts containing rat CEA raises the possibility that human CEA may be immunogenic in man. Treatment with heat, proteolytic enzymes and periodate oxidation revealed that rat CEA, similar to human CEA contained both carbohydrate and protein epitopes. The epitopes shared by rat and human CEA that were detectable by the monkey anti-human CEA serum appeared to be carbohydrate, whereas the epitopes on rat CEA with which the rat mAb combined appeared to be protein, and those detected by the rabbit anti-rat CEA serum appeared to be carbohydrate, as well as protein. These studies also indicated that, although the rat, rabbit and monkey produced antibodies specific for rat CEA, the epitopes detectable by antibodies from one species appeared to be distinct from those detectable by antibodies from the other two species. These observations have important implications in studies on human CEA. Its use as a reliable diagnostic marker for malignancy hinges on the detection of tumor-specific epitopes on the molecule. Such epitopes have not yet been clearly identified by antibodies produced in foreign species. Indeed, our finding that the rat mAb to rat CEA bound only to tumor extracts and not to extracts of normal tissues, including intestinal tissues, suggests that human beings would be the most likely source of a tumor-specific antibody to human CEA. In future studies, the role antibodies play in immunity against CEA-positive tumors will be explored and attempts will be made to determine whether all of the serologically detectable epitopes on rat CEA can induce tumor resistance, or whether this activity is limited to epitopes detectable only by rat antibodies. This information could have important implications in the use of human CEA in the immunotherapy of malignancies.