Although precipitating antibody is associated with human hypersensitivity pneumonitis, there is evidence that cell-mediated hypersensitivity may be involved in disease pathogenesis. In this study, interstitial, and peribronchial lesions were produced by respiratory challenge of rabbits passively sensitized with ovalbumin-sensitive lymph node cells. Ovalbumin sensitivity of donor rabbits and lymph node cells was demonstrated by skin testing, migration inhibition factor (MIF) production using alveolar wash cells as migrating cells, and lymphocyte stimulation. Passive cell transfer was accomplished by intraperitoneal injection with all lymph node cells obtained from one donor transferred to one recipient. Recipients were challenged by aerosol or intratracheal injection of antigen immediately or 24 hr after passive sensitization and were killed 48 hr after challenge. Lesions in rabbits passively sensitized by lymph node cells and challenged with antigen by intratracheal inoculation consisted of focal pneumonitis with intra-alveolar edema and infiltrates of mononuclear cells in alveoli and alveoli septa. Aerosol challenge of passively sensitized animals produced similar changes, but peribronchial tissue containing macrophages and germinal centers was prominent in this group. Antiovalbumin serum recipients challenged by intratracheal injection demonstrated only mild peribronchial mononuclear cell infiltrates, without pneumonitis. Control animals receiving lymph node cells only or challenge only demonstrated no changes in lung histology.