The role of gender in the pathogenesis of Alzheimer's disease (AD) is an important issue that remains controversial. We compared men and women in late-onset familial AD kindreds for the risk of developing AD by studying 26 well-characterized familial AD kindreds from the Oregon Alzheimer Disease Center and, for confirmation, an additional 32 kindreds from the National Cell Repository (NCR) at the Indiana University Alzheimer Disease Center. Comparing women to men, the age-adjusted odds ratio estimates were 3.2 (p = 0.0002) for the Oregon data and 2.3 (p = 0.004) for the NCR data. These results suggest that gender is an independent risk factor for familial late-onset AD and may play a role in the pathogenesis of this disease.