Kidney and patient survival of 351 consecutive patients undergoing first cadaveric renal transplants since 1968 were reviewed to determine the effects of splenectomy on outcome. Special emphasis was given to analysis of 106 splenectomized and 102 nonsplenectomized patients treated since 1975. During the first two years after transplant, kidney survival was better in the splenectomized patients, with no adverse effect on patient survival. However, after the first two years, patient survival became significantly worse in splenectomized patients (35.5% vs. 60.5% at 84 months). Of the deaths, infection was the cause in 26.7% of nonsplenectomized patients compared with 50% of splenectomized patients (P< 0.07). Of patients alive at one year posttransplant, death rates were not different in patients splenectomized before 1975 or after 1975. Timing of splenectomy (prior vs. concurrent) had no effect on outcome. The adverse effect of splenectomy on mortality appeared to be more pronounced in younger (≤ 45 year-old) than in older (> 45 year-old) patients. Splenectomy should not be performed routinely in preparation for a cadaveric transplant because of an unacceptably high late mortality that is primarily from sepsis.