Cyclosporin A (CY A) is a hydrophobic, undecapeptide, fungal metabolite with potent immunosuppressive effects on T lymphocyte-mediated immune responses. Suppressor T lymphocytes generated during a mixed leukocyte reaction (MLR) performed in the presence of CY A, release a factor that suppresses a primary MLR of responder T cells, which is derived from the same strain as the factor producer but lacks specificity for the stimulator cell. These results suggest a finely regulated pathway by which CY A may induce and maintain a permanent state of transplantation tolerance in vivo.