Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease leading to progressive cell death of upper and lower motor neurons and reactive astrogliosis. Two proteins which may be relevant in this respect (tau and S100 beta) were studied in cerebrospinal fluid (CSF) next to routine parameters in 20 patients with sporadic ALS and 20 age-matched controls. Serum levels of creatine kinase (CK) were also determined to monitor the muscular involvement. S100 beta showed a significant decrease in CSF over the disease course (P=0.024). CSF tau as well as serum CK were elevated in 70% of the ALS patients. While highest CSF tau levels were found rather in the early disease stages, serum CK showed a shift of the peak values to several months later. Elevation of the CSF/serum albumin quotient occurred in 20% of the cases most likely representing a non-specific finding in ALS.