Geographic regions characterized by income inequality are associated with adverse mortality statistics, but the pathophysiologic mechanisms that mediate this ecologic relationship have not been elucidated. This study used a United States mail survey of 34158 male and 42741 female healthy-adult volunteers to test the association between residence in geographic regions with relative income inequality and the likelihood of weight gain at the waist. Respondents came from 21 states that were characterized by the household income inequality (HII) index, a measure reflecting the proportion of total income received by the more well off 50% of households in the state. The main outcome measure was self-reported weight gain mainly at the waist as opposed to weight gain at other anatomic sites. After controlling for age, other individual-level factors, and each state's median household income, men's likelihood of weight gain at the waist was positively associated (p = 0.0008) with the HII index. Men from states with a high HII (households above the median receive 81.6% to 82.6% of the income) described weight gain at the waist more often than men from states with a low HII (households above the median receive 77.0% to 78.5% of the income) (odds ratio = 1.12, 95% confidence interval 1.03 to 1.22). Women's results showed a non-significant trend in the same direction. An association between ecologically defined socio-environmental stress and abdominal obesity may help to clarify the pathophysiologic pathways leading to several major chronic diseases.