A candidate neuroprotective agent for neurodegenerative disorders is erythropoietin (EPO). We measured EPO in cerebrospinal fluid (CSF) and serum of patients with amyotrophic lateral sclerosis (ALS). Patients with ALS (N=60), Alzheimer's disease (AD, N=20) and age-matched controls (N=33) were included. Patients with ALS included 30 patients who showed a rapid progression of disease, and 30 patients that showed a slower progression. EPO was measured using ELISA technique. We found CSF EPO levels to be lower in ALS as compared to AD and controls (p<0.05), while no differences were found with regard to serum levels. Patients with ALS who showed a rapid disease progression had lower CSF EPO levels compared to those who progressed more slowly (p=0.03). Low CSF EPO in ALS may imply that the EPO-associated capacity to protect neurons from degeneration is impaired in ALS. Low concentrations of CSF EPO seem to point towards a rapid progression of disease that may be associated with a poorer prognosis.