Severe non-missile head injury commonly results in a form of brain damage known as diffuse axonal injury (DAI). The histological diagnosis of DAI is made by silver staining for the presence of axonal retraction balls. This feature takes about 24 h to develop and does not allow for the early histological diagnosis of DAI. We have used immunocytochemistry for the beta-amyloid precursor protein (beta APP) as a marker for axonal injury in formalin-fixed, paraffin-embedded sections of human brain. Axonal beta APP immunoreactivity was present in all cases which had survived for 3 h or more. This was true even where the degree of head injury did not appear to be severe, supporting the theory that DAI is a severe form of a more common phenomenon of axonal injury which occurs after cerebral trauma. beta APP immunoreactivity was also found in some non-head injured cases and so cannot be considered to be a specific marker for trauma. The results show that beta APP immunocytochemistry may be useful in the detection of traumatic axonal injury in its early stages, before the formation of axonal retraction balls, provided care is taken to exclude other causes of such immunoreactivity.