Advances in the dialysis technique and increasing urea Kt/V have not improved outcomes for end-stage renal disease patients maintained on hemodialysis (HD) therapy. Attention has, thus, focused on enhancing solute removal via prolonged HD sessions. A reduction in the serum levels of phosphorus and β-2-microglobulin (B2M) with longer HD treatments has been linked to improved patient outcomes. We have shown that serum phosphorus levels are significantly lowered in patients maintained on thrice-weekly, in-center, 8-hour nocturnal HD performed at a blood flow rate of 400 mL/min. The kinetics of this modality were examined. A total of 8 patients participated in the study (age 45±7 years). Serum creatinine levels decreased from 9.2±1.9 to 3.0±1.0 mg/dL at 8 hours while serum phosphorus decreased from 5.7±1.9 to 2.5±0.7 mg/dL at 8 hours. The initial decrease from predialysis values to 1 hour after the start of HD was significant for both creatinine (P<0.0001) and phosphorus (P<0.001). Serum B2M decreased from 26.8±5.5 mg/L predialysis to 14.9±7.0 mg/L at 8 hours (P<0.01). Dialysate-side clearances of phosphorus and creatinine were 136±13 and 143±27 cm3/min, respectively. Phosphorus clearances were steadily maintained during the 8-hour session. A total of 904±292 mg of phosphorus was removed during the 8-hour treatment, with 501±174 mg (55%) removed during the first 4 hours and the remaining 45% continuously removed during the latter one-half of the session. The overall calculated B2M clearance was 55.1±40.3 cm3/min using the immediate post-B2M value and 28.4±34.2 mg/L using the 30-minute postdialysis value for the calculation. Serum levels of phosphorus and B2M decrease dramatically during an 8-hour session. Future studies are necessary to determine whether the enhanced solute removal with longer HD sessions translates into an improved outcome for HD patients.