Health literacy has emerged as an important factor related to health in older persons. The reason for the link between health literacy and health outcomes is not clear. Possible explanations include common relations among income, education, access to health care, health-promotion behaviors, frequency of reading, and perceptual impairments. In this study we investigate the relation of health literacy to self-reported health status and explore the impact of these explanatory variables on this relation in persons aged 40 years and older who participated in the 2003 U.S. National Assessment of Adult Literacy (NAAL). Using regression models, we evaluated the impact of potential explanatory variables on the relation of health literacy to self-reported health status. Regression models confirmed previously-observed relations of health literacy, age, income, and education to health. The inclusion of income and education significantly decreased the relation of health literacy to health. While other variables, such as health maintenance and preventive health behaviors, were significantly related to health, they did not change the relation of health literacy to health. Even after taking multiple explanatory variables into account, the relation between health literacy and health status remained significant, suggesting that they alone do not completely account for the observed relation. Some other factor or combination of factors may account for the relation of health literacy to health. (Contains 7 tables.)