Push/pull hemodiafiltration is characterized by alternate filtration and backfiltration, while sterile pyrogen-free dialysate is flowing through a hemodiafilter. During the filtration phase, uremic substances are eliminated not only by diffusive, but also by convective transport. During the backfiltration phase, dialysate is quickly pushed to the blood side (i.e. backfiltration) so as to make up for the excessive reduction in body fluid that has developed during the immediately preceding filtration phase. In the most recently improved version of push/pull hemodiafiltration, the body fluid replacement volume is over 120 liters during a 4- hour treatment. This replacement of a large amount of body fluid may be due to the increased filtration rate in the hemodiafilter resulting from failure of the complete formation of a protein gel layer on the blood side surface. The filtration time in push/pull hemodiafiltration is so short that the also short backfiltration to follow may take over before the protein gel layer is completely formed on the membrane surface. Since the filtration and backfiltration times are much shorter in push/pull hemodiafiltration than the time for blood to pass through the hemodiafilter, it is concentrated and diluted many times (approx. 25 times) before it leaves the hemodiafilter. Therefore, push/pull hemodiafiltration is functionally similar to a predilution hemodiafiltration. The reduction rate of beta-microglobulin was greater by push/pull hemodiafiltration than by hemodialysis, when a high-flux polysulfone hemodiafilter was employed. However, the difference in the reduction rate was rather small between them, because of the improved hemodiafilters, which remove so much beta2-microglobulin only by dialysis. Nevertheless, restless legs syndrome, irritability, insomnia and pruritus were alleviated after switching the treatment modality from hemodialysis to push/pull hemodiafiltration. This may indicate that these symptoms are caused by the accumulation of uremic substances larger than beta2-microglobulin.