An antigen expressed by most human cells, but not erythrocytes, has been defined by a murine monoclonal antibody, TRA-2-10. This antigen is expressed on the surface of human-mouse somatic cell hybrids, and segregation analysis indicates that it is controlled by a gene located on human chromosome 1. From lysates of most human cells, surface-labelled with 125I, TRA-2-10 immunoprecipitates two polypeptides with molecular weights in the range of about 55 000 to 73 000 depending upon the cell line. Since the TRA-2-10 polypeptides from a fibroblast cell strain and a hepatoma cell line from one individual differ, we conclude that the observed difference in molecular weight has an epigenetic origin.