It is apparent that occupational exposure to cotton dust, and in vivo exposure to its components, may result in a number of cellular and humoral events. These include specific antibody formation, mediator release, complement activation, endotoxin effects, and related phenomena. The role of these, either singly or in combination, in the pathogenesis of cotton dust-induced lung disease awaits elucidation. Provocative inhalation challenge studies, using well-characterized standard cotton dusts with careful monitoring of physiologic effects, and in vitro assays will provide answers to some of these questions. Development of a suitable animal model would prove to be invaluable for studying the etiology of the disease and might permit evaluation of the relationship of the acute disease to any chronic effects. It is likely that several pathogenetic mechanisms may be found to be operative and that other, as yet untested, effects such as activation of arachidonic acid metabolism may play an important role in the development of this disease.