Purpose: Endotoxin, a component of gram-negative bacterial membranes, is commonly seen in agricultural and industrial environments with high levels of exposure to organic dusts or fibers. Animal models show modulation of the innate immune response by early life exposure to endotoxin, and both early and later life organic dust exposures have been shown to influence atopic disease in humans. We undertook analyses to examine the association of early life f81m exposures and adult occupational organic dust exposure with SLE. Methods: Recent]y diagnosed SLE patients (11=265) were identified from university and community-based rheumatology practices in the southeastern United States. Age and sex-matched controls (n=355) were recruited from state driver's license registries. Lifetime agricultural and work histories were obtained by questionnaire. Organic dust exposure was inferred through self-reported experience with various crops, work in textiles, hog or poultry processing, and paper product 01' furniture manufacture. Adjusted odds ratios (Adj. OR) and 95% confidence intervals (CI) were estimated by logistic regression models including age, sex, state, race, and education. Results: Experience on a farm was common in this population (43% of patients lived or worked on a farm during childhood and 14% as adults), but was not associated with SLE overall. Among those who ever lived 01' worked on a farm, childhood experience on farms raising livestock was inversely associated with SLE (Adj. OR=0.57, 95% CI 0.33, 0.79), as was adult experience on a farm raising grain 01' com (OR=0.41, 95% Cl 0.19, 0.92; and 0.50,95% CI 0.25, 0.99). Work in a textile mill or factory was also common (24% of patients) and in never-smokers was inversely associated with SLE (Adj. OR=0.38; 95% CI 0.21, 0.70). Other occupational sources of organic dust were not associated with SLE risk. Conclusions: The observed associations imply a lower risk of SLE with some types of organic dust exposure, including childhood experience on fal111s raising animals and adult experience on farms raising grain or com. Adult work in the textile industry was also inversely associated with SLE in never-smokers. Further analyses will involve more specific assessment of exposures in textile jobs, the relationship of textile exposures and smoking habit, and the timing of exposure prior to disease onset. In sum, these findings support the idea that in some settings endotoxin or other components of organic dust exposure may protect against the development of SLE.