PURPOSE: Inheritance of a particular apolipoprotein E gene polymorphism, the epsilon4 allele, has been associated with elevated risk for Alzheimer's disease and a poor outcome following head injury. The neuronal injury associated with Alzheimer's disease and brain injury may have a number of similarities with the nerve cell changes associated with glaucoma. Thus, we have investigated the association of inheritance of apolipoprotein E allelic isoforms (epsilon2, [epsilon]3, and epsilon4) with relative risk for different forms of glaucoma. METHODS: Apolipoprotein E genotype was examined in a Tasmanian population sample comprised of glaucoma sufferers with elevated or normal intraocular pressure and compared to a control sample of elderly Tasmanians without glaucoma. RESULTS: Approximately twice as many normal tension (38.0%) and high tension (34.2%) glaucoma cases possessed an epsilon4 allele compared to control cases (18.9%). The odds of epsilon4 carriers having normal tension glaucoma were significantly greater than for epsilon3 homozygotes (odds ratio 2.45, 95% confidence interval [1.02-5.91]) even after adjusting for age and gender (odd ratio 2.87 [1.02-8.05]). The increased odds of high tension glaucoma among [epsilon]4 allele carriers were not significant (adjusted odds ratio 1.53 [0.64-3.68]). CONCLUSIONS: The data indicate that, in the Tasmanian population, inheritance of the [epsilon]4 allele is associated with elevated risk for glaucomatous changes that are not related to increased intraocular pressure.