A water-soluble polysaccharide-protein complex isolated from cotton dust was found to be the major histamine-releasing component of the dust using an in vitro system with human and pig lung. The polymer also released lysosomal enzymes from the lung of these two species but not from that of the rat. At a concentration of 0.4 mg/ml of medium, the polymer caused tissue necrosis in explants of human foetal lung maintained for 8 days in culture. These findings are important in considering the pathogenesis of byssinosis.