The results of 61 cadaveric allografts preserved for 30 to 76 hours were analyzed to determine the effect of cold ischemia time, the method of preservation, and the type of immunosuppression on early graft viability and long-term graft survival. Preservation in cold storage up to 50 hours gave a low incidence of nonfunction (4%) and of posttransplant dialysis (20%) and a high rate of function both at 1 month (96%) and at 2 years (60%). Cold ischemia time greater than 50 hours caused a significantly increased need for dialysis (58%) but without appreciable difference in graft function at 1 month or at 2 years. Preservation by machine had no advantage over preservation by simple cold storage when the cold ischemia time was less than 50 hours. When cold ischemia time exceeded 50 hours, machine preservation was associated with a significantly reduced incidence of posttransplant dialysis but without significant differences in long-term function at 2 years. With up to 50 hours of cold ischemia and providing there was no ATN, CsA had little nephrotoxicity and gave excellent graft function at 1 month and at 2 years. However, the nephrotoxicity of CsA was markedly increased when the preservation interval exceeded 50 hours, resulting in a significantly increased rate of primary nonfunction and the need for dialysis with a significant decrease in graft function at 1 month and at 2 years. The nephrotoxicity of CsA was considerably decreased or eliminated without affecting its powerful immunosuppressive property when initial immunosuppression was begun with azathioprine with sequential conversion to CsA when graft function was fully established. It is recommended that when cold ischemia is long or when there is ATN, CsA should be used as a sequential therapy to azathioprine after graft diuresis or, alternatively, in much smaller doses as part of a combination therapy with azathioprine.