In patients with end-stage renal disease (ESRD), viral or bacterial infections are postulated to abolish or impair response to recombinant erythropoietin (Epogen). However, previous reports revealed that response to Epogen among hemodialysis patients with a particular viral infection-human immunodeficiency virus (HIV)-seems to be variable and is independent of illness severity. To further explore the issue of response to Epogen in hemodialysis patients with viral infection, we retrospectively studied four patients with hepatitis B virus infection over a 3 month period to compare their response to Epogen and endogenous erythropoietin levels with those of a control group of patients without hepatitis B virus infection. Weekly predialysis hematocrit, and monthly serum albumin concentration, transferrin saturation as well as percent reduction of urea were obtained from patient records, and mean values were calculated for each subject. Mean age of the patients (n = 4) was 63 +/- 7.5 years compared with 55 +/- 23 years for the control subjects (n = 4)(p = 0.02). The mean hematocrit of the study patients was 33.7 +/- 2.8% compared with 34.7 +/- 4.9% in the control subjects (p = 0.49), and the mean endogenous erythropoietin level in the study patients was 27 +/- 22 mIU/ml compared with 5.7 +/- 1.9 mIU/ml in the control group (p = 0.001). The mean dose of thrice weekly Epogen, both at onset of the study and when endogenous erythropoietin was measured, was 61 +/- 19 U/kg body weight in the patients, compared with 74 +/- 8 U/kg body weight in the control subjects (p = 0.002). We conclude that patients with ESRD and hepatitis B surface antigenemia respond to Epogen as well as their counterparts without hepatitis B virus infection. in addition, patients with hepatitis B surface antigenemia have much higher serum levels of endogenous erythropoietin and require less exogenous erythropoietin injections than their counterparts.