β-Amyloid (Aβ) deposits are found in the brains of approximately one-third of patients who die within days after a severe head injury; their presence correlating strongly with possession of an apolipoprotein E (apoE)-ε4 allele. The aim of the study was to investigate the relationship between Aβ42, Aβ40 and apoE immunostaining of Aβ plaques in the cerebral cortex and the relevance of apoE genotype in 23 fatally head-injured patients. These cases were known to have Aβ deposits from a previous study in which they were examined and semiquantified and related to apoE genotype. In the present study, the temporal cortex was probed using four different antibodies that recognize Aβ42(43), Aβ40 and an antibody to apoE. Aβ42(43)-positive plaques were observed in all of the 23 cases and Aβ40 immunoreactivity in only 11 of the 23 cases. In addition, semiquantitative analysis showed that relatively fewer plaques were detected with anti-Aβ40 than anti-Aβ42(43). ApoE-immunoreactive plaques were identified in 18 of the 23 cases. The number of plaques stained for apoE was relatively less than for Aβ42(43) but greater than for Aβ40. Furthermore, the density of Aβ plaques detected using either Aβ42(43), Aβ40 or apoE antibodies was associated with possession of apoE-ε4 in an allele dose-dependent manner. The results are consistent with Aβ42(43) as the initially deposited species in brain parenchyma and provide evidence that apoE is involved in the early stages of amyloid deposition. Further, the findings may be of relevance to the role of apoE genotype in influencing outcome after acute brain injury.