The immunosuppressive mechanism of Deoxymethylspergualin (MeDSG) on human lymphocyte responses in vitro was assessed in comparison with Cyclosporin A (CyA). Peripheral blood mononuclear cells from normal human volunteers were used for assay of mixed lymphocyte reaction (MLR), cell-mediated lympholysis (CML) and blastogenesis by PHA and OKT3. MeDSG suppressed only allogenic stimulation (MLR and CML), however, CyA showed a suppressive effect for all assays. Kinetic study of MLR showed that the suppressive activity did not decrease even when MeDSG was added at day 3 or day 4. CyA, however, showed a weak suppressive effect when added at a later phase of MLR. The results suggest that MeDSG is a useful immunosuppressive agent and, in vitro, its immunosuppressive mechanism on human lymphocyte responses is quite different from CyA.