The concentration changes, during hemodialysis treatment, of 18 characteristic uremia compounds, analyzed by high-pressure liquid chromatography in sera of renal patients were studied. Pre- to postdialysis concentration ratios (dialysis ratio, D) varied from 0.83 to 3.04 for the different solutes. A division into three solute groups, on the basis of their D values, could be rationalized qualitatively from data on protein binding and dialyzer clearance. One group showed low dialysis ratios which could be explained from plasma protein binding. The second group had intermediate D values, comparable to those of creatinine. For some of the members of the third group, high D values might indicate a compartmentalization and resistance to mass transfer across biological membranes. Among the latter are the tubularly secreted hippuric acid and p-hydroxyhippuric acid. For most of the (protein-bound) solutes, protein binding was shown to decrease during hemodialysis. Protein binding levels were higher after dialysis only for hippuric acid and the as yet unidentified fluorescent solute designated UFK8. In conclusion, the change of serum concentrations and of protein binding resulting from hemodialysis treatment are presented and are compared for 18 accumulating solutes in sera of patients with end-stage renal failure.