High S100B serum levels are considered to reflect brain injury severity. However, the dynamics of S100B passage from the cerebral compartment into the blood remain unclear. We examined the temporal profile of S100B release into the cerebrospinal fluid (CSF) and blood in acute brain injury.In patients treated with ventricular drainage (subarachnoid hemorrhage, SAH, n = 23; traumatic brain injury, TBI, n = 19), we measured S100B levels in the serum and CSF. The Glasgow Coma Score (GCS) was assessed daily. Statistical analysis was performed by the Mann-Whitney rank sum test for group differences and by the Pearson correlation.In normal controls (n = 6), S100B levels in the serum (0.05 +/- 0.01 microg/L) comprised around 10% of the CSF concentration (0.66 +/- 0.08 microg/L). Following brain injury, S100B levels were significantly increased in the serum (p < 0.05 in SAH day 2-5, TBI day 1-8) and excessively increased in the CSF (p < 0.05 in SAH and TBI day 1-10). For the individual patient, there was no consistent correlation between S100B levels in serum or CSF and GCS. We therefore calculated the ratio of S100B serum/CSF. Following brain injury, the S100B passage from the CSF to the blood was significantly impaired. Further, higher ratios were correlated with better neurological function (p = 0.002).Because stimulated active S100B release may serve as a repair mechanism, a higher S100B serum/CSF ratio may contribute to neurological recovery.