Deposition of amyloid beta-protein (A beta) in the brain plays a key role in the pathogenesis of Alzheimer's disease. Head injury is an epidemiological risk factor for Alzheimer's disease, and deposition of A beta occurs in approximately one third of individuals dying shortly after a severe head injury. Of the three common apolipoprotein E alleles (APOE-epsilon 2, epsilon 3, and epsilon 4) APOE-epsilon 4 allele is a strong risk factor for both sporadic and some familial cases of Alzheimer's disease and there is in vitro evidence that apolipoprotein E is directly involved in A beta deposition. We have examined the frequency of APOE-epsilon 4 in those individuals with A beta deposition following head injury and found that the APOE-epsilon 4 frequency (0.52) is higher than in most studies of sporadic Alzheimer's disease. In those head-injured individuals without amyloid deposition the APOE-epsilon 4 frequency (0.16) is similar to that in non-Alzheimer's disease controls (p < 0.00001). Our data indicate an interaction between known environmental and genetic risk factors for Alzheimer's disease and underlines the importance of convergence of data around the common mechanism of A beta deposition. Furthermore, it indicates a genetic susceptibility to the effects of a head injury which may be of significance both to those who have recently sustained such an injury and to those whose activities put them at risk of trauma.