Eight chronic, anuric hemodialysis patients were randomly treated with a high-flux polysulphone dialyzer (F80), using 6 different modes: conventional bicarbonate hemodialysis (HD), hemodiafiltration (HDF) with a replacement solution at 40, 60, 80 or 100 ml/min in postdilution and 80 ml/min in predilution. The differences in β<sub>2</sub>-microglobulin (β2M) reduction ratio and clearance were evaluated statistically by analysis of variance (ANOVA). Both studies revealed no significant difference between HD and HDF40 in postdilution, but an increasing significant difference from HDF60 to HDF100 in postdilution and with HDF80 in predilution. The mean reduction ratio ranged from 49.7 (HD) to 72.7% (HDF 100 ml/min), showing an overall statistically significant difference (p = 0.0000). For the clearance, the range was between 63.8 (HD) and 116.8 ml/min (HDF 100 ml/min) (p = 0.0000). β2M in the effluent dialysate with HDF100 ml/min reached up to a mean of 258 mg/session. Concerning small molecules (BUN, creatinine and P), there was a statistically significant different clearance for creatinine and especially for P with HDF 100 ml/min. Conclusion: HDF with an on-line replacement solution at 100 ml/min and a high-flux and biocompatible polysulphone membrane represents a new tool for enhanced removal of β2M. Besides a significant increase in creatinine and especially in phosphorus clearance is noted.