We compared epoetin alfa (EPO) dose requirements and hematocrit response in 17 patients receiving chronic hemodialysis at baseline and after 3 and 12 months of therapy with angiotensin-converting enzyme (ACE) inhibitors (12 enalapril, 5 captopril). No acute processes were present (infection, hemorrhage, inflammation) at time of starting ACE inhibitor therapy. Mean (+/- SD) intravenous EPO dosages at zero, 3, and 12 months were 6012 +/- 2575, 5800 +/- 2026, and 5660 +/- 2285 U 3 times/week (p=0.56), and mean differences were -212 U for 0-3 months (95% CI -1310 to 886) and -713 U for 0-12 months (95% CI -2142 to 716). Mean +/- SD hematocrits were 30.5 +/- 3.9%, 31.6 +/- 3.2%, and 34.2 +/- 3.1% (p=0.01, zero vs 12 mo), and mean differences were 1.7% for 0-3 months (95% CI -1.41 to 4.81) and 3.85% for zero-12 months (95% CI 0.71-7). Our results indicate that ACE inhibitors do not increase EPO dose requirements or reduce hematocrits in these patients.