The clinical significance of leukocyte reduction of all blood components must be deducted from patients transfused in the surgical setting. Under these circumstances many factors contribute to morbidity and mortality, while such factors can be candidates for confounders. Moreover, to investigate effects on infrequent events such as post-operative mortality and multiple organ dysfunction syndrome, large patient cohorts must be studied. Our studies suggest that leukocytes or leukocyte aggregates in red cell transfusions indeed may be harmful if larger dosages are administered under certain clinical circumstances. A critical leukocyte load seems to start with approximately 2.5 x 10(9). Reducing the leukocyte contamination of red cell components, not necessarily by filtration, may benefit patients who require multiple transfusions within a short time interval.