In order to improve the biochemical reactivity of the cellulose polymer, which is mainly attributed to the presence of surface hydroxyl groups, derivatized cellulosic membranes have been engineered replacing or masking some or all of the hydroxyl groups in the manufacturing process of the membrane. The present study was set up to analyze both biocompatibility and functional performance of two different derivatized cellulosic membranes (cellulose diacetate; polyethylene glycol, PEG, acid-grafted cellulose) as compared to a synthetic membrane (polymethylmethacrylate, PMMA). Cellulose diacetate is prepared by substituting hydroxyl groups with acetyl groups; PEG cellulose is obtained by grafting PEG chains onto the cellulosic polymer with a smaller amount of substitution than cellulose diacetate. While the three dialyzers provided similar urea and creatinine removal, the dialyzer containing cellulose diacetate showed a reduced ability to remove 32-microglobulin compared to that containing PEG cellulose or PMMA. A transient reduction in leukocyte count was observed for both derivatized cellulosic membranes. The neutrophil and monocyte counts throughout the entire dialysis session showed a closer parallelism with the cellular expression of the adhesive receptor CD 15s (sialyl-Lewis x molecule) than with CD11b/CD18 expression. Platelet activation, as indicated by the percentage of cells expressing the activation markers CD62P (P-selectin) and CD63 (gp53), occurred with all membranes at 15 min of dialysis and also with PMMA at 30 min. An increased formation of platelet-neutrophil and platelet-monocyte coaggregates was found at 15 and 30 min during dialysis with cellulose diacetate and PMMA but not with PEG cellulose. Generally in concomitance with the increase in platelet-neutrophil coaggregates, an increased hydrogen peroxide production by neutrophils occurred. Our results indicate that derivatizing cellulose may represent a useful approach to improve the biocompatibility of the cellulose polymer, though some homeostatic reactions remain activated. Our results also indicate that there may be a great variability in the biocompatibility profile of derivatize cellulosic membranes which most likely stem from the different type of structural modification rather than from the degree of hydroxyl group replacement.