Recent efforts to identify the bronchoactive agents in cotton dust have precipitated a host of studies on isolated cells such as platelets, neutrophils, alveolar machrophages and pulmonary artery endothelial cells, as well as isolated tissues such as airway smooth muscle and tracheal epithelium. Aqueous extracts of cotton dust (CDE) contain a potent 5-HT receptor agonist capable of stimulating smooth muscle directly. CDE also contain tannin, which cases platelet aggregation, as well as release of 5-HT and thromboxane, both of which are powerful smooth muscle constrictors. CDE cause the release of NCF, PGF (2 ) and interleukin-1 from alveolar machrophages. Tannin and endotoxin isolated from cotton dusts and bracts also cause the release of NCF and PAF from alveolar machropbages, respectively. In order for any agent to effect changes in smooth muscle tone, it must cross the airway epithelium and, if platelets are involved, the pulmonary endothelium as well. CDE decrease the resistance of the isolated tracheal epithelium and increase the paracellular mannitol flux. CDE and tannin also cause time and concentration dependent changes in the morphology of cultured pulmonary artery endothelial cells. Thus, CDE may activate airway smooth muscle, platelets, and neutrophils via both direct and indirect mechanisms indicating the importance of cell-to-cell interactions. The end result may be release of mediators from a variety of cells that are capable of contracting not only smooth muscle but smooth muscle in the pulmonary and bronchial circulations as well.