Optimizing solute removal at minimized albumin loss is a major goal of dialyzer engineering. In a prospective, randomized, crossover study on eight patients (age 63 +/- 14 years) on maintenance hemodialysis, the new Baxter Xenium 170 high-flux dialyzer (BX), which contains a 1.7-m(2) PUREMA H dialysis membrane, was compared with two widely used reference high-flux dialyzers currently available for hemodialysis in North America, the Fresenius Optiflux 180 NR (FO) and the Gambro Polyflux 170 H (GP). Solute removal and biocompatibility were assessed in hemodialysis for 240 min at blood and dialysate flow rates of 300 and 500 mL/min, respectively. Additional ex vivo experiments detecting the interleukin-1beta (IL-1b) generation in recirculated donor blood were performed to demonstrate the pyrogen retention properties of the dialyzers. The instantaneous plasma clearances were similar for the three dialyzers except for cystatin c (cysc), for which a lower clearance was measured with FO as compared with BX and GP after 30 and 180 min of hemodialysis. The reduction ratios (RRs) corrected for the hemoconcentration of beta(2)-microglobulin and cysc were lower in FO (44 +/- 9 and 35 +/- 9%, respectively) versus BX (62 +/- 6 and 59 +/- 7%, respectively) and GP (61 +/- 7 and 56 +/- 8%, respectively). The RRs of the cytokine tumor necrosis factor alpha and interleukin-6 were not different between the dialyzers. The albumin loss was <300 mg for all filters. No differences between the dialyzers were found in the biocompatibility parameters showing very low leukocyte and complement activation. The ex vivo recirculation experiments revealed a significantly higher IL-1b generation for GP (710 +/- 585 pg/mL) versus BX (317 +/- 211 pg/mL) and FO (151 +/- 38 pg/mL). BX is characterized by a steep solute sieving profile with high low-molecular weight protein removal at virtually no albumin loss and an excellent biocompatibility. This improved performance may be regarded as a contribution to optimal dialysis therapy.