The allocation of cadaver kidneys for transplantation should have two objectives: a fair distribution of kidneys among the waiting recipients and a high success rate. Currently, organ exchange organizations are following mainly a policy of success oriented allocation in that the kidneys are distributed according to the best achievable HLA match. A consequence of this policy is that patients with rare HLA phenotypes experience prolonged waiting times and that there are large kidney exchange imbalances among transplant centers. Based on theoretical considerations, we described previously the selection routine COMB which was aimed at decreasing excessive waiting times. In this study we present an extension of this routine called XCOMB which builds on realistic conditions according to the current Euro-transplant waiting list. This new procedure decreases the average and maximum waiting time, adjusts for rare HLA phenotypes and HLA homozygosity, provides for a reasonably balanced kidney exchange rate among centers, and guarantees an HLA match distribution and overall transplant success rate near the theoretically possible optimum. The program was tested in an extensive simulation based on actual data derived from 35,000 cadaver kidney transplants. Although more complex than procedures currently in use, the program's efficient software allows the selection of a patient within one second from a waiting list of 10,000 potential recipients, using readily available computer hardware.