Airway challenge with cotton bract extract (CBE) causes reversible bronchospasm in most volunteers never before exposed to CBE or the textile industry. Lung function abnormalities develop slowly after inhalation with a maximum effect reached within 2 hours and lung function slowly improving thereafter. When CBE was injected intradermally in three naive subjects with negligible airway response to CBE, we observed an initial wheal-and-flare reaction within minutes followed by erythema and subsequent induration that persisted for 24 to 48 hours. Microscopic examination of skin biopsy specimens obtained during the course of these reactions revealed edema in the early phase followed by perivascular infiltration of a mixed cellular nature in the subsequent stages of the reaction. Degranulation of mast cells was noted throughout the course of the reaction. These findings indirectly suggest that a nonspecific inflammatory reaction initiated by mast cell-derived mediators and sustained by the presence of infiltrating cells may be responsible for some of the airway effects observed in byssinosis.