To examine effects of dialyzer membranes and anticoagulants on hemodialysis (HD)-triggered neutrophil degranulation. We measured plasma myeloperoxidase (MPO) and elastase (ELT) by an enzyme-linked immunoabsorbent assay. During routine HD with a cuprophane membrane and high molecular weight (HMW) heparin, plasma MPO was rapidly upregulated to maximal levels within 15 min after starting extracorporeal circulation. In contrast, the level of plasma ELT gradually increased such that the highest level was achieved at the end of the procedure. When polysulfone and polymethylmethacrylate membranes were substituted for cuprophane, the rise in ELT was markedly suppressed. Polysulfone was also capable of reducing the MPO response, although the effect was less prominent than that for ELT. As for anticoagulants, nafamostat mesylate (NM) completely suppressed the rise in plasma MPO during HD with cuprophane. Low molecular weight (LMW) heparin also partially inhibited this response. In sharp contrast, there was no significant difference in the ELT response between nafamostat, HMW, and LMW heparins. Thus, NM maximally suppressed the rise of plasma MPO but had no effect on the ELT response. Our results suggest that neutrophil degranulation of MPO and ELT is differentially regulated during HD. Polysulfone and NM appear to maximally reduce excessive neutrophil activation.