IN a previous publication we hypothesized that Alzheimer's disease (AD) can be induced by the age-related increase in expression of β-amyloid precursor protein (βAPP) in the medial temporal lobe. Head injury has also been identified as a risk factor for AD, and as such, similarities should exist between the pathology found after head injury, and the earliest stages of pathology in AD. In this study, we have quantified the number of βAPP-immunoreactive neurones in the medial temporal cortex (pre-α cells, layer II) of 13 head injured, and 17 control patients. Significantly more βAPP immunoreactive neurones were observed in head injury cases (mean 18.4 per cluster) compared with controls (mean 13.4 per cluster, p < 0.05). These data provide a mechanism to explain how an environmental event such as head injury can generate the same molecular pathology (increased neuronal βAPP) as is found in the earliest stages of AD.