Recombinant human erythropoietin (epoetin) is a remarkably safe and effective biological product. Many dialysis patients are benefiting from the use of this drug when administered intravenously (IV) or subcutaneously (SC) three times a week. However, many patients are not receiving optimal therapy. Optimal therapy requires an understanding of the principles of effective usage and a definition of an optimal hematocrit (Hct) level. These therapeutic principles include (1) the erythroid response to epoetin is dose-dependent, but variable within a given dose;(2) the SC route of injection is as effective, if not more so, than IV injections;(3) the frequency of administration is route-dependent;(4) adequate iron stores are necessary for optimal response;(5) blood pressure may increase as the Hct increases, but may improve with time due to hemodynamic adjustments;(6) the anemia is primarily a hormone-deficiency state and not due to uremia; and (7) infections and traumatic (ie, surgical) inflammation may blunt the response to epoetin. Many patients with the anemia of renal failure have yet to benefit from treatment. These include patients with progressive renal failure or chronic transplant rejection, and dialysis patients who have had incomplete correction of their anemia.