Recent advances in the development of immunosuppressive agents, including newer immunophylin drugs such as FK-506 and lymphocyte DNA synthesis inhibitors such as RS-61443, have allowed rapid progress to be achieved in the prevention and treatment of allograft rejection. Soon, these drugs will join cyclosporine and OKT3 as significant advancements in our battle against allograft loss and dysfunction caused by rejection. Newer developments in immunosuppressive therapy depend on our ability to understand how the immune system works in mediating allograft destructive events. Therefore it is critical that our basic understanding of immunologic mechanisms be incorporated into the development and use of current and future immunosuppressive agents.