BACKGROUND: Erythropoietin (EPO) requirement to reach a specified target hemoglobin level varies in patients on dialysis, the reasons being multifactorial. Angiotensin II has been shown to stimulate proliferation of early erythroid progenitors via erythropoietin and the plasma level of angiotensin II has been strongly associated with angiotensin converting enzyme (ACE) gene polymorphism. EPO resistance index (ERI, weekly rhEPO dose/hematocrit/body weight) is a collective responsiveness between EPO and hematocrit. We have evaluated whether ACE gene polymorphism might exert effect on ERI and also have analysed various laboratory parameters that could affect erythropoietin requirement in HD patients. METHODS: We have compared various demographic data and laboratory parameters, including age, sex, months on dialysis, body mass index (BMI), EPO requirement, ERI, high sensitivity C-reactive protein (hsCRP), ferritin, albumin, hematocrit, iPTH, Kt/V, normalized protein catabolic rate (nPCR), cause of renal failure and whether or not patients were on ACE inhibitor or Angiotensin receptor blocker (ARB), in 199 patients on hemodialysis therapy [M: F 94: 105, Age 61+/-13, duration of dialysis 63 (3-287 months)] according to ACE gene polymorphism (II, ID, DD). We also have assessed independent association of ERI with demographic variables and laboratory parameters using linear regression analysis. RESULTS: There was statistically significant difference (p=0.034) in ERI in the II/ID group compared to the DD group and it was lower in the DD group. But there was no statistically significant difference in other demographic data and laboratory parameters according to ACE gene polymorphism. In the linear regression analysis, lower BMI (p<0.001), female gender (p=0.001), and ACE gene polymorphism (non-DD vs. DD, p=0.027) were determined to be independent factors affecting high ERI. CONCLUSION: ACE gene polymorphism could be determining factor of EPO requirement in patients on hemodialysis. Improving nutritional status might be helpful in reducing EPO requirement and we should consider the gender difference in determining EPO dose in patients on hemodialysis.