Normal subjects were exposed for several hours either in a mill or to cotton dust clouds generated in the laboratory. The acute responses included an increase in respiratory rate, airways resistance, residual volume, functional residual capacity and the frequency dependence of dynamic compliance. The peak flow, forced expiratory volume and forced vital capacity were reduced. No dose response relationship was observed between the fall in forced expiratory volume and the concentration of the respirable airborne dust over the range 1 to 5 mg/cubic metre approximately, when inhaled for 4 hours, although there was an extremely small rise in airways resistance. Histamine excretion measured as the urinary metabolite 1-methyl-4-imidazole acetic acid was doubled compared with control values. The respiratory effects of the inhaled dust lasted several days, whereas although aqueous extracts produced similar responses recovery was complete within hours. Inhalation of cotton washed in 20% alcohol 80% water, produced less increase in histamine release and minimal lung function changes. E-coli endotoxin inhaled in doses greater than those associated with work in a cotton full produced a smaller increase in airways resistance than the experimental cotton dust clouds.