ABSTRACT: We have established two monoclonal antibodies (TM7-3 and TM3-8) that react to choriocarcinoma cells. Both of these monoclonal antibodies have shown a similar reactive pattern to human cell lines, normal and neoplastic trophoblast tissues, and other fetal and adult tissues. They have reacted to nine of the ten choriocarcinoma cell lines, as well as to Hela cells (a cervical carcinoma cell line). During a cellular radioimmunoassay, neither TM7-3 nor TM3-8 reacted to two T lymphoblastoid cell lines or three B lymphoblastoid cell lines. Immunofluorescence and immunoper-oxidase staining showed that both monoclonal antibodies reacted selectively to the cytotrophoblast-like tumor cells of a choriocarcinoma and a hydatidiform mole but not to syncytiotrophoblast-like tumor cells. TM7-3 and TM3-8 also reacted slightly to the normal cytotrophoblast of early human chorionic villi under the same conditions as they did to choriocarcinoma tissue, but not to syncytiotrophoblast. In various normal tissues, TM7-3 and TM3-8 bind only to a part of the urinary tubles of the kidney and to the ducts of the pancreas of both adult and fetus.