We have previously used guinea pig tracheal rings to analyze the effect of cotton and other organic dusts on airway smooth muscle (ASM) contraction. In a recent epidemiologic study we documented that workers exposed to dust in the tobacco industry developed a high frequency of respiratory symptoms and ventilatory changes similar to those of textile workers. Recent studies with pharmacologic agents using a water soluble extract of tobacco dust (TDE) demonstrated that TDE causes ASM contraction by non-immunological mechanisms involving mediators. Clinical studies suggest that the airways of allergic individuals may be particularly prone to the effects of environmental agents. In order to study this question we used our guinea pig model and TDE. Dose related contractions of nonsensitized and sensitized (ovalbumin injected) guinea pig tracheas (GPT) were demonstrated. Tracheal tissues were studied with and without epithelium. Using this model we demonstrated that sensitization of GPT enhances the response to TDE. Removal of the epithelial layer significantly diminishes the TDE response in both sensitized and nonsenstized GPT. Removal of the epithelium from senstized GPT reduces its response to that seen in nonsensitized GPT with the epithelium intact. We suggest that the enhanced effect in sensitized GPT is mediated primarily through the inflamed epithelium.