Platelet interaction with neutrophils may occur to a significant degree during hemodialysis (HD). We have recently shown that the enhanced neutrophil reactive oxygen species (ROS) production during the early phase of HD with cuprophan (CUP) is sustained by neutrophils which have bound platelets through P-selectin (CD62P). The evaluation of platelet-neutrophil interactions during dialysis offers the novel aspect of cell-cell interactions as a new parameter for studying the biocompatibility of dialyzer membranes. By the use of flow cytometry techniques, the present study was set up to analyze intradialytic platelet-neutrophil coaggregate formation and neutrophil ROS (hydrogen peroxide) production from 6 HD patients each dialysed with CUP, cellulose diacetate (CDA), polymethylmethacrylate (PMMA), and polyacrylonitrile (PAN) in a cross-over clinical trial. Platelet-neutrophil coaggregate formation (percentage of neutrophil cells positive for CD62P) and ROS production by neutrophils (total population; CD62P+ cells; CD62P- cells) were determined before HD and after 10', 20'and 40'. CD62P+ neutrophils significantly increased during HD with CUP (10', 20', 40'), PMMA (20') and CDA (20), while no change was observed with PAN. The difference between CUP and the other membranes was significant at 10', 20' and 40'; at 20', PMMA vs PAN p<0.005. ROS production by total neutrophil population significantly increased with CUP (10', 20), PMMA (20) and CDA (20'). The increase with CUP was higher at 10' when compared to CDA (p<0.020) or PAN (p<0.005), and at 20' versus the other three membranes; at 20' PMMA vs PAN p<0.005. Only neutrophils gated in neutrophil-platelet coaggregate areas (CD26P+ neutrophils) produced hydrogen peroxide. ROS production by CD62P+ neutrophils significantly increased with CUP (10', 20), PMMA (20') and CDA (20'). The increase with CUP was significantly (p<0.0002) higher than the other three membranes at 10' and 20'; at 20', PMMA vs PAN p<0.02. With each membrane, ROS production by CD62P- neutrophils showed no significant change at any time point during HD. The results of the present study indicate that interactions between platelets and neutrophils can mediate some pathophysiological abnormalities associated with hemodialysis treatment. Our data show that cellulose diacetate, a modified cellulosic membrane, exhibits a biocompatibility profile in terms of platelet-neutrophil interactions improved as compared to the parent cellulose membrane and comparable to that of some synthetic membranes. Our data also show that there is considerable variability in the biocompatibility of synthetic membranes. Though cellulosic membranes are generally considered as being less biocompatible than synthetic membranes, our results indicate that classification of membranes by biocompatibility is more complex than a simple division into cellulosic and synthetic membranes, especially with the advent of modified cellulosic membranes.