Acute spirometric responses to inhaled cotton dust were examined in a population of 226 healthy, non-asthmatic adults whose atopic status had been evaluated by skin prick tests to 10 common environmental allergens. Exposure to cotton dust occurred in model cardrooms where elutriated dust levels were carefully controlled (1.02 mg/m3). Atopy, defined as positive prick tests to at least two allergens, was observed in 26% of subjects. Significant forced expiratory volume in one second (FEV1) decrements occurred after exposure to cotton dust independent of atopic status (p less than 0.001). The mean FEV1 decline in atopic subjects, however, was significantly greater than in non-atopic subjects (p less than 0.05). Degree of atopy, as measured by number of positive skin tests, also exhibited a significant association with cotton induced decrements in FEV1 (p less than 0.05). These data suggest that atopy may be an important determinant of the magnitude of the acute pulmonary response to cotton dust. This may reflect the non-specific airways hyperresponsiveness that has been described in non-asthmatic, atopic individuals.