The capacity of sorbent systems to increase solute clearances above the levels that are provided by hemodialysis has not been well defined. This study assessed the extent to which solute clearances can be increased by addition of a sorbent to the dialysate. Attention was focused on the clearance of protein-bound solutes, which are cleared poorly by conventional hemodialysis. A reservoir that contained test solutes and artificial plasma was dialyzed first with the plasma flow set at 46 ؎ 3 ml/min and the dialysate flow (Q d ) set at 42 ؎ 3 ml/min using a hollow fiber kidney with mass transfer area coefficients greater than Q d for each of the solutes. Under these conditions, the clearance of urea (Cl urea ) was 34 ؎ 1 ml/min, whereas the clearances of the protein-bound solutes indican (Cl ind ), p-cresol sulfate (Cl pcs ), and p-cresol (Cl pc ) averaged only 5 ؎ 1, 4 ؎ 1, and 14 ؎ 1 ml/min, respectively The effect of addition of activated charcoal to the dialysate then was compared with the effect of increasing Q d without addition of any sorbent. Addition of charcoal increased Cl ind , Cl pcs , and Cl pc to 12 ؎ 1, 9 ؎ 2, and 35 ؎ 4 ml/min without changing Cl urea . Increasing Q d without the addition of sorbent had a similar effect on the clearance of the protein-bound solutes. Mathematical modeling predicted these changes and showed that the maximal effect of addition of a sorbent to the dialysate is equivalent to that of an unlimited increase in Q d . These results suggest that as an adjunct to conventional hemodialysis, addition of sorbents to the dialysate could increase the clearance of protein-bound solutes without greatly altering the clearance of unbound solutes. S olute uptake by sorbents long has been considered a possible treatment for uremia (1-4), but the extent to which sorbents can increase solute clearances above the levels that are obtained by hemodialysis remains uncertain. In most sorbent systems, blood is separated from the sorbent by a semipermeable membrane to avoid the adverse effects of direct blood-sorbent contact. Solutes therefore must diffuse through the membrane before binding to the sorbent. Our study sought to define better the capacity for solute clearance of this two-step process. We first modeled the effect of adding a sorbent to the dialysate when dialysis is carried out by countercurrent flow of plasma and dialysate on opposite sides of a semipermeable membrane. The predicted effect of a sorbent in this case is to lower the free solute concentration in the dialysate, and adding a sorbent to the dialysate can increase solute clearances to the same extent as increasing dialysate flow (Q d ).One potential application of sorbents is to increase the clearance of solutes that bind to plasma proteins. These solutes are cleared poorly by conventional hemodialysis (5-9). Moreover, although not conclusive, a variety of evidence suggests that protein-bound solutes contribute to uremic toxicity (5,6,10 -12), and mathematical modeling predicts that the clearance of protein-bound solutes c...