Cotton mill dust contains a complex mixture of compounds derived from the cotton plant as well as contaminating bacteria and fungi, Components of the fungal cell wall are well recognized as activators of alveolar macrophages (AM0). Zymosan, a particulate product of yeast cell walls, is a potent stimulator of arachidonic acid (AA) metabolism in AM0. Zymosan contains both -1,3-glucan and a-mannan polymers and macrophages contain distinct receptors for each type of polymer. To determine whether stimulation of the glucan or mannan receptor was responsible for the subsequent release and metabolism of AA, rabbit AM0 preloaded with [(14)C]-AA were challenged with zymosan, particulate -1,3-glucan derived from yeast cell walls, soluble glucan from barley and soluble mannan from yeast and the release of [(14)C]-AA was measured. Only zymosan and particulate glucan were found to be stimulators of AA release. Thus, activation of resident AM0 by the -1,3 glucans present in fungal cell wall fragments in the cotton mill dust could contribute to the production of AA metabolites found in the airways of exposed subjects.