Tannin, isolated from cotton bracts and implicated in the pathogenesis of byssinosis, inhibits Cl- secretion in isolated bovine tracheal epithelial cells, desensitizes airway cells to isoproterenol stimulation and decreases -adrenergic receptor surface density. We have hypothesized that tannin exposure in cotton bracts results in a cycle of desensitization of the airway epithelial -adrenergic receptor with partial recovery upon removal from the environment. We have also hypothesized that this cycle of desensitization/partial recovery results in the downregulation of the -adrenergic receptor and this downregulation contributes to the pathogenesis of byssinosis. In these studies, increasing duration of exposure to tannin inhibited isoproterenol-stimulated cAMP release and the inhibition was reversible after 24 h. Repetitive (3 days), cyclical (8 h) exposures to tannin were associated with increasing inhibition of isoproterenol-stimulated cAMP release with partial recovery and incremental decreases in -adrenergic receptor surface number. Tannin exposure (25 µg/ml for 24 h) also decreased -adrenergic receptor mRNA. We conclude that tannin exposure downregulates the -adrenergic receptor and results in increasing desensitization with repetitive exposure.