Under normal physiological conditions red blood cell production is controlled primarily by erythropoietin, although multiple additional stimulatory factors are likely to be involved. One of these factors, angiotensin II, can modulate erythropolesis directly via its type 1 receptor, as well as indirectly through multiple secondary mediators. We propose that angiotensin II exerts its stimulatory effect during the early stages of erythropoiesis, and that this effect serves as an important compensatory mechanism if erythropoietin production is chronically inadequate. We speculate that if this compensatory stimulation continues to be abnormally high after restoration of erythropoietin production following renal transplantation, erythrocytosis ensues. © 2004 Elsevier Inc. All rights reserved.