OBJECTIVES: The aim of this investigation was to study the relationship between delusions and depression in Alzheimer's disease (AD). DESIGN: This was a cross-sectional, case control study. SETTING: Neuropsychiatry Service, the Johns Hopkins School of Medicine, USPARTICIPANTS: 303 community-residing patients with probable AD according to NINCDS/ADRDA criteria were included in the study. Seventy-five patients with delusions only were compared to a control group of 228 patients who had neither delusions nor hallucinations. Patients with only hallucinations or both delusions and hallucinations were excluded. MEASURES: Patients were assessed clinically for the presence of delusions using the DSM-IV glossary definitions. They were also rated on standardized measures of depression, cognitive impairment, staging of dementia, general medical health, and functional impairment. RESULTS: There was an association between delusions and depression among patients with AD. Before adjustment for other variables, the presence of depression conferred a 1.8-fold (95% confidence intervals (CI) = 1.0-3.1; p = 0.04) higher risk of delusions. After adjustment for multiple other variables, this risk increased further to 6.8-fold (95% CI = 2.1-21.6; p = 0.001). CONCLUSIONS; Delusions in AD are strongly associated with depression after statistical adjustment for all confounding variables, which might distort this association. This finding has implications for our understanding of the etio-pathogenesis and management of delusions and depression in AD