Allelic frequencies of apolipoprotein epsilon 4 were compared in 13 dizygotic twin pairs and 13 sibling pairs in which at least one member has Alzheimer disease (AD). Among discordant pairs of twins and siblings, frequencies were significantly greater in affected than intact partners. There was no significant difference in allelic frequencies between twins with a positive family history and twins with a negative family history. The epsilon 4 allele was more common in the sibling sample selected for family aggregation of AD than the twin sample. Several lines of evidence indicate that while the epsilon 4 allele appears to be one risk factor for AD, other etiological factors must be considered as well.