Specific antibody-secreting hybridomas have been obtained by fusing Syrian or Armenian hamster (Mesocricetus auratus or Cricetulus migratorius) spleen cells with mouse myeloma cells. The hamsters were immunized to mouse cytolytic T lymphocytes. Hybrids were selected either by an indirect binding assay using an 125I-monoclonal antibody (MAb) reactive with hamster kappa-chains or by their ability to block T cell-mediated cytolysis. Three hybridoma clones were obtained that secreted intact IgM-like and IgG-like hamster MAb as shown by SDS-PAGE. The clones were stable as shown by subcloning. Two MAb recognized antigens of wide tissue distribution; the third bound specifically to T lymphocytes, gave strong inhibition of T cell-mediated cytolysis, and immunoprecipitated the Lyt-2,3 molecule.