Animal model studies of the etiology of hypersensitivity pneumonitis are reviewed. The studies used guinea pigs, rabbits, cattle, rats, dogs, and monkeys. Animal models reviewed demonstrate differences in results based on the use of a soluble antigen or a particulate one that may more closely mimic the natural situation; antigens that have not been ascribed to the growing list of agents causing hypersensitivity pneumonitis; or unnatural methods of immunization. The author concludes that further elucidation of the interactions of inhaled antigens and the complement system is needed. He recommends additional efforts to determine the direct actions of fungal toxins on the respiratory tract, the irritant effects of particulate dusts, and the contributory effects of the microbial flora.