Major depression afflicts from 15% to 31% of patients with Alzheimer's disease (AD). The charts of 137 patients with AD were reviewed to assess the association between several variables and the risk of developing major depression. Thirty-eight patients (28%) had major depression. A family history of mood disorder was associated with a significantly increased risk for major depression, but this was only true in women (relative of odds = 2.82,95 confidence interval from 1.19 to 6.69). There was no relationship between major depression and a personal history of depression, younger age at onset of AD, history of substance use disorder, institutionalization, and marital status. These results suggest that the relationship between family history and depression in AD is more complex than previously thought.