Kidneys transplanted to HLA-DRw6+ recipients have been shown to have an inferior graft survival compared with DRw6- patients. Because pretransplant blood transfusions influence kidney graft survival, we investigated whether the number of blood transfusions contributes to the observed poor graft survival in DRw6+ patients. We have found that the difference in graft survival in DRw6+ and DRw6- recipients may be explained by a blood transfusion policy that is disadvantageous for DRw6+ recipients. Thus, graft survival in DRw6+ recipients was excellent for those who had received only a single transfusion. More transfusions resulted in a gradual decrease in graft survival. When the number of transfusions exceeded 5, graft survival improved again. By contrast, DRw6- recipients showed an improvement in graft survival with an increasing number of transfusions. DRw6+ recipients therefore display inferior graft survival only when they receive 3-5 transfusions. This finding provides a possible explanation as to why the "DRw6 effect" is a controversial issue, and it suggests that DRw6+ recipients should be given a different pre-transplant transfusion protocol than DRw6- patients.