A model of hypersensitivity pneumonitis (HP) in syngeneic animals would allow experiments designed to determine immunopathogenesis of HP. Strain II guinea pigs were treated with Micropolyspora faeni and challenged with intratrachael M. faeni. Lung histology 4 days thereafter was quantitatively evaluated. Intratrachael administration of M. faeni caused interstitial and intraalveolar collections of mononuclear and polymorphonuclear cells. Sensitized (pretreated with M. faeni) animals’ lungs had more extensive pathology than unsensitized animals. 3 weeks after challenge with M. faeni, pulmonary histopathology regressed to granulomatous interstitial infiltration, similar to that found in chronic HP in humans. We conclude that the pulmonary histopathologic response of sensitized strain II guinea pigs to intratrachael M. faeni resembles human HP.