BACKGROUND:Elevated body mass index (BMI) and arsenic are both associated with cancer and with non-malignant lung disease. Using a unique exposure situation in Northern Chile with data on lifetime arsenic exposure, we previously identified the first evidence of an interaction between arsenic and BMI for the development of lung cancer. OBJECTIVES:We examined whether there was an interaction between arsenic and BMI for the development of non-malignant lung disease. METHODS:Data on lifetime arsenic exposure, respiratory symptoms, spirometry, BMI, and smoking were collected from 751 participants from cities in Northern Chile with varying levels of arsenic water concentrations. Spirometry values and respiratory symptoms were compared across subjects in different categories of arsenic exposure and BMI. RESULTS:Adults with both a BMI above the 90th percentile (>33.9kg/m2) and arsenic water concentrations ≥11µg/L exhibited high odds ratios (ORs) for cough (OR = 10.7, 95% confidence interval (CI): 3.03, 50.1), shortness of breath (OR = 14.2, 95% CI: 4.79, 52.4), wheeze (OR = 14.4, 95% CI: 4.80, 53.7), and the combined presence of any respiratory symptom (OR = 9.82, 95% CI: 4.22, 24.5). In subjects with lower BMIs, respiratory symptom ORs for arsenic water concentrations ≥11µg/L were markedly lower. In never-smokers, reductions in forced vital capacity associated with arsenic increased as BMI increased. Analysis of the FEV1/FVC ratio in never-smokers significantly increased as BMI and arsenic concentrations increased. Similar trends were not observed for FEV1 alone or in ever-smokers. CONCLUSIONS:This study provides preliminary evidence that BMI may increase the risk for arsenic-related non-malignant respiratory disease.