Evidence from animal, human cross-sectional, case-control, and prospective studies indicate that hormone replacement therapy (HRT) is a promising treatment to delay the onset of symptoms of dementia. The Women's Health Initiative Memory Study (WHIMS) is the first double-masked, randomized, placebo-controlled, long-term clinical trial designed to test the hypothesis that HRT reduces the incidence of all-cause dementia in women aged 65 and older. WHIMS, an ancillary study to the Women's Health Initiative (WHI) funded by the National Institutes of Health, will recruit a subgroup of women aged 65 and older from among those enrolling in the HRT trial of the WHI. The WHI clinical centers and 10 affiliated satellites plan to enroll approximately 8300 women into WHIMS over a 2-year period. Participants will be followed annually for 6 years, receiving cognitive assessments via the Modified Mini-Mental State (3MS) Examination. Women who screen positively for cognitive impairment on the basis of an educational and age-adjusted 3MS cutpoint proceed to more extensive neuropsychological testing and neurologic evaluation. Each woman suspected to have dementia then undergoes a series of laboratory tests that confirm the clinical diagnosis and classify the type of dementia. WHIMS is designed to provide more than 80% statistical power to detect a 40% reduction in the rate of all-cause dementia, an effect that could have profound public health implications for older women's health and functioning.