There is evidence that high frequency, as well as long duration, hemodialysis provides better clinical outcomes. We developed nocturnal hemodialysis, a new innovative form of renal replacement therapy, which is performed six to seven nights per week for 8 to 10 h during sleep at home. Blood flow was set at 300 ml/min and dialysate flow at 100 ml/min. An internal jugular catheter was used as the vascular access. Special precautions were taken to prevent accidental disconnection during sleep, as well as air embolization. Dialysis functions from the patient's home were monitored continuously via a modem at the nocturnal hemodialysis center. Twelve patients have completed training and have been successfully performing nocturnal hemodialysis for up to 34 mo. This study represents 170 patient months of experience accumulated over 3 yr. There was hemodynamic stability and significant subjective improvement in patient well being. Nightly Kt/V was 0.99. Weekly removal of phosphate was twice as high and beta2 microglobulin 4 times as high as conventional hemodialysis. All patients have discontinued their phosphate binders and have increased dietary phosphate and protein intake. BP control was achieved with fewer medications. Dialyzer reuse has decreased the operating costs to the level of the other form of home dialysis. Complications were infrequent and were related primarily to the dialysis access. Nocturnal hemodialysis represents the most efficient form of dialysis at low cost and should be considered as an option for patients who can be trained for home hemodialysis.