Technical Abstract: The prevalence of household food security, which reflects adequacy and stability of food supply, has been measured periodically in the U.S. and occasionally in high-risk groups or specific regions. Despite a plausible biological mechanism to suggest negative health outcomes of food insecurity, this relationship has not been adequately evaluated. This study was conducted in the Lower Mississippi Delta region to examine the association between household food insecurity and self-reported health status in adults. A two-stage stratified cluster sample representative of the population in 36 counties in the Delta region of Arkansas, Louisiana, and Mississippi was selected using list-assisted random digit dialing telephone methodology. After households were selected and screened, a randomly selected adult was interviewed within each sampled household. Data were collected to measure food security status and self-reported mental, physical, and general health status, using the US Food Security Survey Module and the Short Form 12-item Health Survey (SF12). Data are reported on a sample of 1488 households. Adults in food insecure households were significantly more likely to rate their health as poor/fair and scored significantly lower on the physical and mental health scales of the SF12. In regression models controlling for income, gender and ethnicity, the interaction between food insecurity status and race was a significant predictor of fair/poor health and lower scores on physical and mental health. Household food insecurity is associated with poorer self-reported health status of adults in this rural, high risk sample in the Lower Mississippi Delta.