Neuron-specific enolase (NSE) is among the biochemical markers in cerebrospinal fluid reported to be useful in the differential diagnosis of Creutzfeldt-Jakob disease from other dementing illnesses. In a group of 58 patients with definite and probable Creutzfeldt-Jakob disease, NSE concentrations (median 94.0, interquartile range 256 ng/mL) were significantly higher (p < 0.001) than in 26 control patients (9.5, 15.5 ng/mL). At a cut-off of 35 ng/mL an optimum sensitivity of 80% with a specificity of 92% for the diagnosis of Creutzfeldt-Jakob disease by NSE in cerebrospinal fluid was obtained.