Protein S-100 is a calcium binding protein, synthetized in astroglial cells in all parts of the central nervous system (CNS). We have previously reported high serum levels of protein S-100 in patients after minor head injury (MHI). A battery of conventional and computerized neuropsychological measures was administered to two groups of MHI patients. Neuropsychological outcome at 12 months postinjury was examined in a group of 7 patients with increased serum levels of protein S-100 after MHI and 7 age- and sex-matched controls without detectable S-100 in serum after MHI. Our results demonstrate no overall cognitive dysfunction in either of the two groups. Our findings indicate specific dysfunction on measures of reaction time, attention and speed of information processing for the S-100 group. Posttraumatic depression does not explain the neuropsychological differences between the groups. These findings support that increased serum levels of protein S-100 may be of predictive and prognostic value for longlasting neurocognitive abnormalities after minor head injury. Presence of S-100 in serum may indicate the presence of diffuse brain damage. Our results suggest that information processing measures in computerized neuropsychological assessment are more sensitive for detecting small signs of neurocognitive abnormalities after MHI than conventional test batteries.