<i>Background/Aims:</i> The contact of blood with artificial surfaces may activate blood leukocytes and platelets and initiate the leukocyte inflammatory response. We have investigated the effect of a hemodialysis (HD) with a cellulosic- and a synthetic-based membrane on circulating leukocyte activation. <i>Methods:</i> Samples were obtained from patients with ESRD at baseline, and at 15 and 120 min of a hemodialysis session from both the arterial and venous lines. Leukocyte respiratory burst was analyzed by luminol chemiluminescence. Actin polymerization, expression of CD11b, and heterotypic aggregation were studied by flow cytometry, leukocyte labeling with NBD phallacidin and monoclonal antibodies, respectively. <i>Results:</i> HD with a cellulosic membrane induced a transient fall in neutrophil (1.2 ± 0.5 × 10⁹ vs. 3.6 ± 0.6 × 10⁹ cells/l; p < 0.05) and monocyte counts (0.2 ± 0.1 × 10⁹ vs. 0.7 ± 0.1 × 10⁹ cells/l; p < 0.05). There was also an increase in respiratory burst in the venous line during a HD with a cellulosic membrane, at 15 and 120 min (100 ± 41 and 143.2 ± 45.3 vs. 23.8 ± 15.7; p < 0.05). Polymerized actin, expressed as fluorescence arbitrary units, was increased in baseline samples from uremic patients versus control subjects (327.8 ± 60.8 for a cellulosic membrane, p < 0.005, and 205 ± 26.5 for a synthetic one, p < 0.05 vs. 97.8 ± 27.6 in controls). The percentage of CD11b+ cells increased in samples during a HD with a cellulosic membrane at the venous line at 15 and 120 min (9.6 ± 4.5 and 18.4 ± 7.1% vs. 3.3 ± 1.9%; p < 0.05%). Changes in heterotypic aggregation during HD did not reach statistical significance, but levels were higher in patients treated with a cellulosic membrane at all points than in patients dialyzed with a synthetic one. <i>Conclusion:</i> There is evidence of a priming state of leukocytes from uremic patients, which is more evident in patients dialyzed with a cellulosic membrane. Cellulosic membranes also induce greater leukocyte activation than synthetic membranes during hemodialysis.