We compared the effect of recombinant human erythropoietin (rhEPO) administration by continuous s.c. infusion (CSI) with that of a weekly bolus s.c. injection (SBI) in five malnourished predialysis anemic patients with diabetic nephropathy. rhEPO was either continuously infused at a flow rate of 6000 IU per week (36 IU/h) (CSI group) or injected s.c. at a dose of 6000 IU once a week (SBI group) for 4 weeks, in a cross-over comparative study with a washout period of 4 weeks. Mean Ϯ S.D. plasma EPO levels increased from a basal value of 18.0 Ϯ 4.9 mIU/ml to a steady state value of 70.5 Ϯ 38.9 mIU/ml 2 weeks after the start of CSI of rhEPO (P < 0.05). Increases in reticulocyte count above the basal value were greater in the CSI group than the SBI group at 3 weeks after the start of treatment (0.94 Ϯ 0.35% vs ¹0.03 Ϯ 0.46%, P < 0.05). Increases in Hb concentration above the basal value were much greater in the CSI group than the SBI group at 4 weeks after the start of treatment (2.56 Ϯ 0.77 g/dl vs 0.28 Ϯ 0.62 g/dl, P < 0.05). These findings suggest that rhEPO administration by CSI is more effective than by SBI for improving anemia in malnourished predialysis patients with diabetic nephropathy.