Studies of cotton textile workers have found an association between atopy and drop in FEV1 over a workshift. We studied the response of previously nonexposed volunteers with and without a history of mild atopy to a 5-h exposure to 1 mg/m3 of respirable cotton dust in a model cardroom. All participants were nonsmokers, had no history of asthma, and had normal spirometry. Twenty atopic subjects gave a personal history of mild respiratory allergy to pollen, dusts, or animals that had been confirmed by a physician. Thirty-two nonatopic subjects had no history of allergy. Spirometry and a methacholine challenge test were performed 1 to 2 days prior to exposure. Spirometry was repeated immediately before exposure to cotton dust; spirometry and a methacholine challenge were performed immediately after exposure. Atopic subjects showed a significantly higher mean serum IgE level to Phadiatop, a screening test to common inhalant allergens, than did nonatopic subjects (mean percent binding, 32.1 versus 1.5; p < 0.001). Atopic subjects had a significantly greater mean fall in FEV1 during exposure (8.3% versus 4.9%, p < 0.05). The difference in FEV1 decline between atopic and nonatopic subjects was similar in magnitude to that reported for workshift FEV1 declines between textile workers with and without mild atopy. Atopic subjects had significantly higher baseline methacholine responsiveness than did nonatopic subjects (26% versus 0% reaching a PD20, p < 0.0005). After cotton dust exposure, there was a significant increase in airway reactivity in both groups (68% versus 20% reaching a PD20, p < 0.0005). For all subjects combined baseline responsiveness was significantly related to the change in FEV1 after exposure.(ABSTRACT TRUNCATED AT 250 WORDS)