Biocompatibility of dialysis membranes is defined, in part, by the tendency to activate the coagulation system. Methods for evaluating stimulation of the coagulation include analyses of markers of platelet activation. The purpose of these studies was to ascertain the effects of high blood flow rates and reprocessing on platelet activation during routine hemodialysis with regenerated cellulose membranes. The platelet alpha-granule protein, beta-thromboglobulin (BTG), was measured in patients undergoing routine chronic hemodialysis with regenerated cellulose dialyzers. Initial studies showed BTG levels to increase from 24 +/- 2 IU/mL at the baseline to 30 +/- 3 IU/mL at 120 minutes and postdialysis, respectively (P < 0.05). In contrast, BTG levels corrected for hemoconcentration with plasma protein concentrations showed no significant changes compared with baseline values. Further studies assessed the effects of two types of new and reprocessed regenerated cellulose dialyzers during four different treatments. Platelet counts at 10 and 30 minutes did not change compared with the baseline, while white blood cell counts decreased significantly. No significant changes in BTG levels occurred when corrected for hemoconcentration with either dialyzer. Additional studies with new and reprocessed regenerated cellulose dialyzers comparing 450 and 220 mL/min blood flow rates at 10 minutes showed no change in BTG. In summary, these studies show no evidence for platelet activation by routine hemodialysis with regenerated cellulose membranes. Differences from previous studies include correction of BTG for hemoconcentration due to ultrafiltration and pre-rinsing of dialyzers. Methods for assessment of cellular activation by dialysis membranes must account for hemoconcentration.