Recombinant human erythropoietin (rHuEPO) treatment has been shown to improve brain and cognitive function in anemic dialysis patients. Significant debate continues, however, regarding the appropriate target hematocrit (Hct) that will lead to the greatest benefits while considering possible side effects and costs of rHuEPO. Current practice results in an Hct averaging only 31% to 32% in dialysis patients, a level less than that achieved in the initial clinical trials and well less than normal. This study was designed to evaluate dialysis patients at the current practice Hct levels versus normal Hct levels (40% to 45%) to see if improvement in brain function resulted. Twenty patients with end-stage renal disease (ESRD) currently being treated with rHuEPO (mean Hct, 31.6%) were administered additional rHuEPO to reach normal Hct levels (mean, 42. 8%). Electroencephalogram (EEG) frequency analysis showed a significant decrease in EEG slowing at greater Hct values, and the auditory oddball and Continuous Performance Task tasks yielded significant electrode and time-by-electrode effects for P300 amplitude. Changes in P300 latency significantly correlated with increased Hct in the auditory oddball task. These findings suggest that further correction of anemia to normal Hct levels may result in continued improvement in neurocognitive function by improving the ability to sustain attention in easier tasks and by enhancing the ability to recognize, discriminate, and hold stimuli in memory for more difficult tasks.