BACKGROUND: High rates of low health literacy among elderly populations along with a high prevalence of chronic conditions may lead to increased levels of depression symptomatology. We sought to determine whether older adults with inadequate health literacy were more likely to report depressive symptoms and whether health literacy was an independent predictor of depression symptomatology. METHODS: A total of 3260 new Medicare enrollees 65 years or older were interviewed in person between June and December 1997 from 4 managed care plans (853 in Cleveland, Ohio, 498 in Houston, Tex, 975 in South Florida, and 934 in Tampa, Fla). Depression symptoms were measured by the Geriatric Depression Scale. RESULTS: Overall, 13% of respondents were classified as depressed. Individuals with inadequate health literacy had 2.7 times the odds (95% confidence interval, 2.2-3.4) of being depressed compared with individuals with adequate health literacy skills. However, after controlling for health status with multiple logistic regression, individuals with inadequate health literacy were not more likely to be depressed (adjusted odds ratio, 1.2; 95% confidence interval, 0.9-1.7). Individuals who had less social support, exercised less than twice a week, drank alcohol heavily, or had poor health status (at least 3 health conditions, physical limitations, or fair or poor self-rated health) had significantly higher odds of depression symptomatology. CONCLUSIONS: Although individuals with inadequate health literacy were more than twice as likely to report depressive symptoms, this was mostly explained by their worse health status. The strong relation between depression symptoms and poor health status suggests the need to research interventions to improve mental and physical health concurrently. The influence of particular interventions on depression, such as referral to community support contacts and recommendations for an exercise program, needs to be further evaluated. Arch Intern Med. 2000;160:3307-3314.