While recombinant human erythropoietin (rHuEPO) is an effective therapy for anemia in renal failure, most published studies concern benefits in relatively healthy hemodialysis patients. The present study compares intravenous and subcutaneous administration of rHuEPO in an unselected group of 128 hemodialysis patients who were randomized to receive rHuEPO in an initial dose of 150 U/kg/week in three divided doses by subcutaneous or intravenous injection. Following a 4-week placebo run-in period, patients received rHuEPO until their hemoglobin was stable between 105 and 125 g/l for 4 weeks and then followed for a further 24 weeks. Eighty-three patients completed the study, 45 in the subcutaneous and 38 in the intravenous group. There was no difference in mean hemoglobin at any stage between subcutaneous and intravenous patients. Mean rHuEPO dose at the time of stabilization was significantly lower in the subcutaneous group compared to the intravenous (205.9 +/- 135.4 vs. 274.1 +/- 142.4 U/kg/week; p = 0.019), mean time to hemoglobin target was 9.9 +/- 4.5 weeks for the subcutaneous group and 11.9 +/- 4.9 weeks for the intravenous group (p = 0.037). Time to stabilization was 14.9 +/- 4.7 weeks for the subcutaneous compared to 17.3 +/- 3.9 weeks for the intravenous group (p = 0.006). Diabetic patients had higher dose requirements for rHuEPO at all time points and required a longer time to reach stabilization than nondiabetics (18.6 +/- 4.6 vs. 15.6 +/- 4.3 weeks; p = 0.016). Quality of life estimated by a disease-specific Kidney Disease Questionnaire improved significantly during rHuEPO therapy in both groups. There was no significant change in dialysis prescription throughout the study.(ABSTRACT TRUNCATED AT 250 WORDS)