Objectives - Oxidative stress and glutamate-mediated excitotoxicity may play an important role in the etiopathogenesis of amyotrophic lateral sclerosis (ALS). Prostaglandin E2 (PGE2) activity can be associated with motor neuron death by inducing free radical formation and glutamate release from astrocytes. The aim of this study was to determine PGE2 concentration in the serum and cerebrospinal fluid (CSF) of ALS patients. Material and methods - PGE2 concentration was measured by the enzyme-linked immunosorbent method in the serum and CSF from ALS and control group patients. Results - Serum and CSF PGE2 concentration was significantly higher in the whole group of ALS patients compared with the control group patients (P < 0.05). There was no relationship between PGE2 concentration and clinical parameters of the disease, such as clinical state, type of ALS onset, and duration of the disease (P > 0.05). A significant correlation between CSF PGE2 concentration and age of control group patients was found (P < 0.05). Conclusions - A significant increase in serum and CSF PGE2 concentration, in ALS patients observed in this study, indicates that PGE2 may play a role in neurodegeneration of ALS through oxidative damage of neurons and glutamate-mediated excitotoxicity. It suggests that inhibition of PGE2 synthesis could prevent motor neuron death. However, serum and CSF PGE2 cannot be a marker of the type of ALS onset, clinical state of patients, or the duration of the disease.