Previous studies have reported that anemia is a frequent occurrence in patients with severe autonomic failure, that it can be corrected by exogenous erythropoietin and that upright blood pressure improves while on erythropoietin. The objective of this study was to determine the alteration of autonomic control during erythropoietin therapy in a patient with severe autonomic failure and severe symptomatic orthostatic hypotension, evaluated by spectral analysis of heart rate variability. The autonomic response to standing was evaluated before, after 1 month and after 6 months of erythropoietin therapy. The results were compared to an age- and sex-matched control adult. There was no improvement in the orthostatic hypotension during and at the end of the erythropoietin treatment despite an increase in hemoglobin from 9.6 g/dl before treatment to 12.5 g/dl during treatment. The spectral estimates of heart rate variability displayed a low variability at baseline, a paradoxical vagal enhancement and a lack of sympathetic increase on standing (before, during and at the end of the treatment). There was no improvement of baseline activity, nor of the response to standing during and at the end of the treatment with erythropoietin. We conclude that erythropoietin did not improve the autonomic response to standing, although it corrected anemia. Erythropoietin did not alter sympathetic activity, as reflected in the low frequency content of the power spectrum of heart rate fluctuations during and at the end of treatment.