A monoclonal antibody, 3D6, identifies a public idiotope or allotope on the human T-cell receptor for antigen, since it not only reacts with the tumor line HPB-ALL, against which it has been raised, but also with 3-13% of peripheral blood T lymphocytes of normal donors. 3D6+ cells have been isolated from an allogeneic mixed lymphocyte culture and cloned by limiting dilution. In this way, allospecific clones were obtained both of the T4+T8- and the T4-T8+ phenotype, which included proliferative as well as cytotoxic cells. Within a panel of 20 cytotoxic clones, different specificities for both class I and class II MHC antigens were found. The clones were tested for their reactivities with four additional anti-T-cell receptor antibodies raised against HPB-ALL. Two of these, 1C1 and 1C2, reacted with all 3D6+ clones. By means of two other antibodies, 2D4 and 65, the 3D6+ receptor family could be divided into four structurally distinct subfamilies. Biochemical analysis suggested that the 1C1, 1C2, 2D4, and 3D6 antibodies define epitopes on the beta chain of the receptor. Isoelectric focusing of receptor molecules isolated from cytotoxic clones with different specificites indicated that there are extensive structural differences in both alpha and beta chains of the receptors. No correlation could be found between the antigenic specificity of a clone and the structure of its receptor in this analysis. It is postulated that the 1C1, 1C2, and 3D6 epitopes may be encoded by a particular germline V beta segment, in analogy with similar, previously described findings in both the human and the murine system.