To assess whether working in a swine confinement facility causes an excess or accelerated decline in lung function, we conducted a population-based study to evaluate the determinants of longitudinal changes in airflow in a population of swine confinement operators. Spirometric measures of lung function were compared between swine confinement operators(N = 168) and neighborhood farmer control subjects(N = 127). Study subjects were randomly selected from a cohort of swine confinement operators in eastern Iowa. The control farming population was matched by geographic location, age, and sex to the swine confinement operators. On average, the follow-up time was approximately 2 yr, with a range of follow-up between 56 and 1,900 d. Although swine confinement operators and neighborhood farmers had similar demographic characteristics (age, gender, racial background, smoking history, and atopy status), swine confinement operators tended to have less farming experience and were more extensively followed (more measures of lung function and longer periods of observation) than the neighborhood farmer control group. Swine confinement operators were also exposed to higher environmental dust concentrations and other irritants than the farmer control subjects. Interestingly, the cross-sectional data indicated that swine confinement operators tended to have slightly lower measures of airflow and greater workshift declines in forced expiratory volume in one second (FEV(1)), forced vital capacity (FVC), and mid-expiratory flow (FEF(25-75)) than the neighborhood farmer control group. After controlling for age, height, gender, cigarette smoking, and follow-up time, longitudinal declines in spirometric measures of lung function were independently related to cross-shift declines in spirometric measures of lung function (FEV(1), FVC, AND FEF(25-75)), higher concentrations of endotoxin present in the bioaerosol (FEV(1) and FEF(25-75)), and working in the swine confinement setting (FEV(1) and FEF(25-75)). Interestingly, cross-shift changes in lung function and higher concentrations of endotoxin in the bioaerosol interacted positively with follow-up time, indicating that these work-related responses and exposures accelerated the decline in FEV(1) and FEF(25-75) during the period of observation. Our results indicate that cross-shift decrements in lung function and higher concentrations of endotoxin are important determinants of accelerated decrements in airflow among agricultural workers. Although work in the swine confinement setting was associated with lower measures of FEV(1) and FEF(25-75) that persisted throughout the period of observation, work in these confinement facilities does not appear specifically to accelerate the progressive loss of lung function among agricultural workers.