Recombinant human erythropoietin (r-huEPO) is now an established therapy for anemia of hemodialysis patients. However, questions remain concerning the optimal maintenance dose as well as the route and frequency of administration. This prospective study was designed to determine whether subcutaneous r-huEPO at a reduced dosage was as effective as intravenous r-huEPO in maintaining constant hemoglobin levels. It involved 12 patients on hemodialysis, previously treated with intravenous r-huEPO for 11.8 +/- 7 months (mean +/- SD). For 3 months hemoglobin was kept at a stable level of 10-13 g/dl with individually titrated intravenous r-huEPO administered thrice weekly after each hemodialysis. Patients were then switched to subcutaneous r-huEPO. Initially, approximately 50% of the previous weekly dose was given as twice weekly subcutaneous injections. During the following 3 months the r-huEPO dosage was adapted to maintain the target hemoglobin level. 3 patients did not complete the second period due to acute intercurrent complications not related to therapy. 9/12 patients completed the study. The hemoglobin concentration was kept at a constant level of (mean +/- SD) 10.5 +/- 1.1, 10.6 +/- 0.9 and 11.1 +/- 0.6 g/dl with 233 +/- 110, 246 +/- 118 and 233 +/- 116 U/kg/week of intravenous r-huEPO for the first 3 months. In the second period hemoglobin was kept at 11.5 +/- 1.2, 11.3 +/- 1.4 and 11.1 +/- 0.9 g/dl with 119 +/- 61, 118 +/- 60 and 137 +/- 78 U/kg/week of subcutaneous r-huEPO. 2 patients required an increase in the r-huEPO dose during the third month of the second period.(ABSTRACT TRUNCATED AT 250 WORDS)