Hemodialysis with cellulose membranes causes a complement-mediated neutropenia. Changes in neutrophil function have also been reported; however, it is unclear if these changes indicate a direct effect of the membrane on neutrophils or if they are a consequence of the neutropenia. We tested the hypothesis that neutrophil oxidative burst activity is enhanced during dialysis with cellulose membranes. Resting and Staphylococcus aureus-stimulated H2O2 production were determined predialysis and in blood entering and leaving the dialyzer during the first 30 min of dialysis and in blood leaving the membrane module in a single-pass on-line model of hemodialysis. Resting H2O2 production increased slightly but significantly during the first 30 min of dialysis. Transit of neutrophils through the dialyzer caused a marked increase in stimulated H2O2 production, indicating priming of the oxidative burst. However, priming was limited to the first 5 min of dialysis before the onset of neutropenia. In contrast, stimulation and priming of H2O2 production persisted throughout 30 min of single-pass on-line perfusion. These results indicate that cellulose membranes both stimulate and prime neutrophil oxidative burst activity but that these effects are partially obscured by neutropenia.