Erythropoietin (EPO) acts as a neuroprotective factor and is upregulated after neuronal injury. It has been reported that in cerebrospinal fluid (CSF) of amyotrophic lateral sclerosis (ALS) patients, the EPO concentration is decreased. In this study, EPO levels in serum and CSF of 30 patients with ALS and in 15 controls, using an ELISA technique, were estimated. EPO level in serum was decreased, especially in patients with bulbar onset ALS. A trend toward a progressive EPO decline with the duration of the disease in the mild + moderate ALS cases was observed. In severe cases, a tendency towards a positive correlation of EPO and duration of the disease was present. Serum EPO values were age related only in mild + moderate ALS in patients below 40 years of age. In CSF, the EPO levels were significantly decreased. Lower EPO values in the bulbar onset ALS when compared with the spinal onset ALS were present. The EPO decrease did not correlate with the severity and duration of the disease. Age relation of the EPO level only in the mild + moderate ALS cases more than 40 years was present. Lack of differences in EPO levels between patients with ALS of rapid and slow progression indicates that EPO concentration cannot be used as a prognostic factor. Nevertheless, the decreased serum and CSF EPO concentration and the known EPO neuroprotective action may indicate that EPO administration can be a new promising therapeutic approach in ALS.