The increasing prevalence and mortality rates of asthma suggest that further investigation is needed to understand modifiable determinants, including occupational and environmental factors. This project provides a unique opportunity for detailed longitudinal study of an inception cohort in a high-risk environment. Aluminum smelter potroom exposures have been strongly associated with an asthma-like illness, yet the incidence, causative agent, risk factors, and natural history of "potroom asthma" remain largely obscure. The project addresses the hypothesis that exposures found in the potroom are associated with the development of increased nonspecific bronchial responsiveness (NSBR), new respiratory symptoms, and occupational asthma. The specific aims are to: 1) determine the incidence of increased (NSBR) and new asthma-like symptoms among newly hired potroom workers; 2) identify cases of verified and possible occupational asthma in the cohort; 3) explore the dose-response relationships of specific potroom exposures with the development of respiratory outcomes; 4) determine the influences of constitutional and behavioral factors (including atopy determined by skin testing, degree of pre-existing NSBR, smoking, and childhood asthma) on the relationships between exposure and respiratory outcomes; and 5) characterize the natural history and pattern of the respiratory problems to gain insight into the mechanism of airway response. An inception cohort of potroom workers will be followed prospectively for five years. Newly hired employees are assessed with questionnaire, spirometry, methacholine challenge, and skin tests for common antigens, prior to beginning potroom work. The questionnaire will be repeated at 2- and 4-months, and all components (except skin testing) will be repeated at 6-months, annually and when an employee separates from work. Detailed exposure assessment is used to develop an individual dose estimate for each cohort member for the exposures of interest. A subset of subjects, including all with increased NSBR or new asthma-like symptoms, will undergo a 2-week detailed assessment of airflow during work and non-work periods using data-logging pulmonary function equipment and concurrent exposure assessment using direct reading (real-time) instruments. Information derived from this cohort can provide a model for understanding the roles of the environment in asthma, as potroom work involves chronic "low-dose" irritant exposures. It capitalizes on a special research opportunity and uses: 1) strict research criteria (requiring a change in symptoms and NSBR) in outcome assessment; 2) concerted efforts to reduce survivor bias; and 3) individual estimates of exposure dose.