The superimposition of human immunodeficiency virus (HIV) infection, associated opportunistic infections, and anti-retroviral therapy further worsens the severity of anemia in patients also suffering from end-stage renal disease. A major cause of anemia in renal failure is a deficiency of erythropoietin. The causes of anemia in HIV disease include direct and indirect stem cell inhibition by the virus, increased peripheral destruction of red blood cells, and bone marrow suppression by various opportunistic infections and therapeutic drugs, particularly zidovudine. We compared the efficacy of recombinant human erythropoietin (rHuEPO) therapy in improving the anemia in HIV-infected end-stage renal disease patients (group I) with that in nondiabetic (group II) and diabetic (group III) hemodialysis patients without HIV infection. All three groups of patients were comparable in dialysis prescription and serum iron studies. Iron supplementation was prescribed to all patients, and none received blood transfusions. After 8 weeks of rHuEPO therapy (administered intravenously in a dose of 100 U/kg body weight thrice weekly), the mean increase in hematocrit was similar in all responders (5.8% increase in hematocrit in 23 of 30 HIV patients and 6.7% increase in 24 of 30 non-HIV patients). Response in hematocrit was noted in HIV patients despite the presence of opportunistic infections in 15 and zidovudine administration in 11. Seven HIV-positive patients and six non-HIV patients failed to respond to rHuEPO. Irrespective of the HIV status, the baseline serum EPO levels in patients responding to rHuEPO were significantly lower than those in nonresponders.(ABSTRACT TRUNCATED AT 250 WORDS)