To test the possible effect of erythropoietin (EPO) induced higher hematocrit on dialysis efficacy and metabolism, 14 metabolically stable hemodialysis patients were evaluated with various kinetic methods, including total dialysate collection. Tests were performed twice before EPO treatment and twice when hemoglobin had stabilized in the targeted range. Samples were frozen and batch analyzed for each patient after completion of the study. During this period, dialysis regimens were fixed. EPO treatment caused several significant changes. Hematocrit increased from 21.5% to 34.3%. Pre- and postdialysis serum potassium increased 0.3-0.4 mmol/l, and 56% more potassium binder was given. Serum phosphate concentrations were unchanged, but the aluminum hydroxide dose had been raised 44%. Dialyzer clearance decreased for urea (4.8%), creatinine (14.7%), phosphate (16.5%) and potassium (8.6%). The ratio of postdialysis/predialysis measurements changed for calcium, creatinine and uric acid. Five patients experienced enhanced appetite, but average dry weight did not change, nor could changes be demonstrated for protein catabolism, generation rate of urea and creatinine, or their distribution volumes. Estimated sodium intake remained unchanged. The findings indicate that EPO treatment reduces dialysis efficiency slightly for a number of substances, but in the metabolically stable patient there are no impressive dietary changes. Problems can be overcome by appropriate changes of dialysis regimen and medication.