The specificity of interactions between mitogenic and non‐mitogenic lectins and disulfide‐linked cell surface receptors on human lymphocytes was explored. Lysates (Nonidet‐P40) of surface‐radioiodinated tonsil lymphocytes and T lymphoblastoid cells (HPB‐ALL) were absorbed with lectin‐agarose derivatives (or bovine serum albumin, BSA‐agarose) or immunoprecipitated with appropriate monoclonal antibodies (mAb). Lectin eluates and solubilized immunoprecipitates were analyzed by two‐dimensional (nonreduced/reduced) sodium dodecyl sulfate‐polyacrylamide gel electrophoresis. Radiolabeled polypeptides were visualized by autoradiography. Among the various lectin‐binding polypeptides, two disulfide‐linked heterodimers (II and III) and two apparent homodimers (I and IV) are bound by pea lectin, con‐canavalin A and lentil lectin on tonsil lymphocytes; II, III and IV are bound both leukoagglutinating (L)‐ and erythroagglutinating (E)‐phytohemagglutinins from Phaseolus vulgaris (PHA). Pokeweed mitogen recognizes only II and III. These molecules are weakly bound by peanut agglutinin, soybean agglutinin, Ulex europaeus agglutinin‐I, Dolichos biflorus agglutinin, Vicia villosa agglutinin and Sophora japonica agglutinin, but are not bound by Helix pomatia agglutinin or BSA‐agarose. Heterodimer II (82–88 kDa), comprized of 50–55‐kDa and 40–43‐kDa subunits, probably represents the α/β T cell antigen receptor (TcRα/β). Heterodimer III (64–72 kDa), comprized of 41‐kDa and 37‐kDa subunits, may represent TcRγ. The homodimers, I (120–130 kDa) and IV (55–61 kDa), comprized of 55–60‐kDa and 30‐kDa polypeptides, respectively, have apparently not been previously described. Evidence that H1‐2D4, a mAb directed against the antigen receptor on HPB‐ALL cells, and E‐PHA interact with a common molecule includes: (a) immunoprecipitation of TcR with H1‐2D4 from the glycopeptide fraction specifically eluted from insolubilized lectin with N‐acetylgalactosamine; and (b) adsorption of TcR from a solubilized H1‐2D4 immunoprecipitate by E‐PHA‐agarose. Recognition of CD3 by E‐PHA is indicated by immunoprecipitation of CD3 protein by UCHT1 from the glycopeptide fraction specifically eluted from E‐PHA. The results are consistent with the view that mitogenic lectins interact with certain disulfide‐linked molecules on human lymphocytes, including the TcR α/β and perhaps TcR γ; while some nonmitogenic lectins also recognize these receptors, the interaction is of low affinity.