Most patients on hemodialysis are treated thrice weekly even if they have residual kidney function, in part because uncertainty remains as to how residual function should be valued and incorporated into the dialysis prescription. Recent guidelines, however, have increased the weight assigned to residual function and thus reduced the treatment time required when it is present. Increasing the weight assigned to residual function may be justified by knowledge that the native kidney performs functions not replicated by dialysis, including solute removal by secretion. This study tested whether plasma concentrations of secreted solutes are as well controlled in patients with residual function on twice weekly hemodialysis as in anuric patients on thrice weekly hemodialysis. We measured the plasma concentration and residual clearance, dialytic clearance, and removal rates for urea and the secreted solutes hippurate, phenylacetylglutamine, indoxyl sulfate, and -cresol sulfate in nine patients on twice weekly hemodialysis and nine patients on thrice weekly hemodialysis. Compared with anuric patients on thrice weekly dialysis with the same standard Kt/V, patients on twice weekly hemodialysis had lower hippurate and phenylacetylglutamine concentrations and similar indoxyl sulfate and -cresol sulfate concentrations. Mathematical modeling revealed that residual secretory function accounted for the observed pattern of solute concentrations. Plasma concentrations of secreted solutes can be well controlled by twice weekly hemodialysis in patients with residual kidney function. This result supports further study of residual kidney function value and the inclusion of this function in dialysis adequacy measures.