The objective of the study was to investigate the validity of outcome prediction after severe head injury using serum levels of S-100B protein and neuron specific enolase. Eighty-two patients with severe head injury were included in this prospective study. Venous blood samples were taken after admission and every 24 h for a maximum of 10 consecutive days. For values of S-100 from 0 to 2.5 micrograms/l, and for values of NSE from 0 to 100 micrograms/l the sensitivity and specificity of incremental values as a predictor of unfavourable outcome were calculated and Receiver Operator Characteristics curves were plotted. Serum S-100 protein was found to be clearly superior to neuron specific enolase in terms of predicting outcome with higher specificity, sensitivity, positive and negative predictive value. According to our experience, S-100B protein represents the most promising serum marker of brain cell damage currently under investigation.