The purpose of this study was to investigate the influence of prolonged treatment with recombinant human erythropoietin (epoetin) on the pharmacokinetics of epoetin in dialysis patients. 12 patients (male/female: 6/6, median age 44 years) with end-stage renal failure were investigated. Five were treated with continuous ambulatory peritoneal dialysis and 7 with haemodialysis. The pharmacokinetics were studied in each patient after an intravenous and a subcutaneous dose of epoetin 100 U/kg before regular treatment with epoetin was instituted. The investigation was repeated in the same patients after a median of 8 months of regular epoetin treatment. The haematocrit count increased from 25 to 33% (medians). The intravenous elimination half-life (8.23vs7.96 hours), intravenous mean residence time (11.8vs11.2 hours), clearance (0.31vs0.32 L/h/1.73 m2), subcutaneous maximal concentration (108vs123 U/L) at 19vs12 hours, and bioavailability (20.8vs21.6%) did not change significantly after prolonged epoetin treatment. The volume of distribution was slightly reduced from 3.76 to 3.46 L/1.73m2. The estimated absorption half-life (25.1vs16.7 hours), the mean input time (29.0vs29.9 hours), and the mean residence time (42.5vs40.1 hours) after subcutaneous application did not change significantly. The estimated endogenous epoetin production was unchanged at 144vs155 U/day/1.73m2. The loss of epoetin in the peritoneal dialysis bags was below 2.3% of the dose.In conclusion, except for a small reduction in the volume of distribution, long term treatment with epoetin had no influence on the intravenous or subcutaneous pharmacokinetics of epoetin in dialysis patients. No compensatory adjustment of the native epoetin production was detected.