Protein-bound solutes are poorly cleared by peritoneal dialysis. We examined the hypothesis that plasma concentrations of bound solutes would therefore rise as residual renal function is lost. Clearances of urea indican and p-cresol sulfate were measured in peritoneal dialysis patients with and without residual function. In patients with residual function, protein binding restricted the peritoneal indican and p-cresol sulfate clearances to 0.3 +/- 0.1 ml/min, as compared to the peritoneal urea clearance of 5.5 +/- 1.1 ml/min. The urinary indican and p-cresol sulfate clearances of 2.7 +/- 2.5 and 1.3 +/- 1.0 ml/min were closer to the urinary urea clearance of 3.9 +/- 2.2 ml/min, reflecting the superior ability of native kidney function to clear bound solutes. Urinary clearance thus provided the majority of the total indican and p-cresol sulfate clearances of 3.0 +/- 2.5 and 1.6 +/- 1.0 ml/min in patients with residual function but the minority of total urea clearance of 9.4 +/- 2.2 ml/min. Loss of residual function lowered the total clearances for indican and p-cresol sulfate to 0.5 +/- 0.2 and 0.4 +/- 0.2 ml/min, whereas the urea clearance fell only slightly. However there was only a modest increase in the plasma indican level and no increase in the plasma p-cresol sulfate level in patients with no residual function because reduction in the daily removal of these solutes accompanied the reduction in their total clearance rates. Reduction in the removal of indican and p-cresol sulfate kept plasma levels from rising markedly when residual function was lost.