BACKGROUND: Farmers have an increased risk of respiratory morbidity and mortality. The causal agents have not been fully established. METHODS: In a cross-sectional study of 4,735 Norwegian farmers, we assessed respiratory symptoms and lung function. Atopy was assessed in a subsample (n = 1,213). Personal exposures to dust, fungal spores, actinomycete spores, endotoxins, bacteria, storage mites, (1-->3)-ss-D-glucans, fungal antigens, organic dust, inorganic dust, silica, ammonia, and hydrogen sulfide were measured for 127 randomly selected farms. RESULTS: Compared to crop farmers, livestock farmers were more likely to have chronic bronchitis (odds ratio [OR], 1.9; 95% confidence interval [CI], 1.4 to 2.6) and COPD (OR, 1.4; 95% CI, 1.1 to 1.7). FEV(1) (-41 mL; 95% CI, -75 to -7) was significantly reduced, but FVC (-15 mL; 95% CI, -54 to 24) was not. Exposure to most agents were predictors of respiratory morbidity, except FVC. Ammonia, hydrogen sulfide, and inorganic dust were most strongly associated in multiple regression models adjusted for coexposures, but the effects of specific biological agents could not be assessed in multiple regression models because they were too highly correlated. Farmers with atopy had a significantly lower FEV(1) (OR, -87 mL; 95% CI, -170 to -7), but atopy was not directly associated with chronic bronchitis, COPD, and FVC. However, the effects of farming and specific exposures on COPD were substantially greater in farmers with atopy. CONCLUSIONS: Livestock farmers have an increased risk of chronic bronchitis, COPD, and reduced FEV(1). Ammonia, hydrogen sulfide, inorganic dust, and organic dust may be causally involved, but a role for specific biological agents cannot be excluded. Farmers with atopy appear more susceptible to develop farming-related COPD.