Evolution of cardiac index in 12 patients with severe renal anemia on regular hemodialysis (hematocrit 19.9 ± 2.8%) was studied during the first 4 months of treatment with recombinant human erythropoietin (rhEPO). At the end of the study period, hematocrit rose to 31.1 ± 3.5% (p < 0.001) and cardiac index significantly decreased (5.34 ± 1.25 vs. 3.81 ± 0.84 liters/min/m2, p < 0.001). Cardiac index fell mainly because of reduction of stroke volume (108 ± 27 vs. 81 ± 25 ml, p < 0.001), while heart rate did not change during the study period. Before starting rhEPO cardiac index was elevated in 11 out of the 12 patients, whereas after 4 months of treatment this was only maintained in 4 of them. We conclude that substitution with rhEPO in hemodialysis patients significantly decreases cardiac index, confirming anemia as the main factor for hyperdynamic circulatory state in these patients. Whether this reduction in cardiac index will ameliorate cardiac morbidity or not and hematocrit levels for achieving the major benefits require further studies.