Apoliprotein E (apoE) is associated with Alzheimer's neurofibrillary tangles and beta-amyloid protein in senile plaques. Recent studies have shown an increased frequency of the epsilon 4 allele of the apoE gene in familial and sporadic cases of Alzheimer's disease (AD). In the present case control study, we have determined the apoE genotype by allele-specific extension of 113 postmortem cases of sporadic AD and 77 control brains shown to be free of AD neuropathological features and then calculated the frequency of the various allelic forms of apoE (epsilon 2, epsilon 3, epsilon 4). The odds ratio associating epsilon 4 with AD was 15.5 (95% confidence interval [CI] 6.2-38.5), and the population attributable risk was 0.53. We have also combined the results of our study and several others to calculate these same parameters in a larger population (570 controls and 961 AD subjects); the odds ratio for this larger group was 6.2 (95% CI 4.9-7.8) and the population attributable risk was 0.57. These results further substantiate and strengthen the association between the epsilon 4 allele of apoE gene and AD. We have also used these results to investigate the usefulness of the determination of epsilon 4 carrier status in the diagnosis of AD.