We have shown that the number of HLA mismatched antigens correlates with the development of new or changes in existing HLA-specific antibodies. We have further shown that the magnitude of the effect varies among groups defined by whether or not HLA-specific antibody was present prior to transplant, by the transplant number, by recipient race, and by donor type. The increases in antibody, which increase with increasing degree of mismatch, result in differences in waiting times reflective of the number of previous mismatches. For many patients, increased waiting time represents not only reduced quality of life but deteriorating health and shortened life expectancy. Globally, increased waiting times translate into increased costs for dialysis, antibody testing, and health care. These factors suggest that HLA matching should not be abandoned but should be given consideration for those patients most affected by mismatches.