Background: Polymorphonuclear leukocytes contain a large number of enzymes and bactericidal proteins stored in granules. Neutrophil activation induces degranulation and immediate release of these bioactive substances, including human neutrophil elastase (HNE) also known as elastase–2 (ELA2), which may contaminate whole blood units and blood components. Materials and Methods: The HNE concentration was determined in the supernatants of blood components with a commercial enzyme–linked immunosorbent assay (ELISA). The effect of leukocyte depletion and storage was evaluated by testing whole blood, buffy–coat–reduced, and leukocyte–depleted red cell units. Buffy–coat–derived platelets and plasma were also tested. Results: HNE concentrations at day 1 were about 50 μg/l in all types of red cell components with the exception of leukocyte–depleted red cells (<0.26 μg/l). In leukocyte–depleted red cells, platelets and plasma, no significant increase was observed during storage. In whole–blood units and buffy–coat–reduced red cells, the HNE concentrations increased steadily and often exceeded 1,000 μg/l when the units expired. Conclusion: Leukocyte depletion may limit the inadvertent infusion of bioactive substances derived from polymorphonuclear leukocytes, of which HNE is but one example. The accumulation of HNE in buffy–coat–reduced red cells may be greater than that of whole blood units. HNE accumulates during storage and its quantity may have pathophysiologic significance. Platelets and plasma derived from buffy coats contain some HNE, but leukocyte–depleted red cells virtually none. However, we consider the accumulation of HNE in these components not to be clinically important. The quantities, kinetics, and occurrence in various blood components of HNE contamination differ from those observed with cytokines.