To evaluate the effects of recombinant human erythropoietin (rHuEPO) on brain function, 15 chronic hemodialysis patients were studied by event-related P300, stimulus-related evoked potentials, and trailmaking before (hematocrit 22.7%) and after rHuEPO (hematocrit 30.6%). P300 peak latency elicited by a tone discrimination paradigm improved (391 before vs. 366 ms after; Cz = vertex; P less than 0.01) confirming beneficial effects on cerebral cognitive processing. P300 amplitude (13.6 vs. 15.8 microV; P = 0.06) and trailmaking tended to improve (55 vs. 43 s). P300 measures were influenced by low hemoglobin levels before rHuEPO (P less than 0.01), suggesting that severe anemia may contribute to uremic brain dysfunction. Furthermore, decrease of stimulus-related auditory brainstem I-V interpeak latency (4.28 before vs. 4.17 ms after; P less than 0.05) and increase of somatosensory N20/P25 amplitude (4.8 vs. 7.0 microV; P less than 0.05) pointed to improvement of sensory pathways by mechanisms unrelated to cognition. Brain dysfunction in chronic hemodialysis patients may, beside other factors, in part be caused by severe anemia and can be improved by rHuEPO treatment.