Rabbits were exposed intratracheally to enzyme 1, a highly immunogenic esterase isolated from Micropolyspora faeni. A single exposure to active enzyme 1 induced no histologically or immuno-histochemically detectable changes in the lungs of experimental animals, while signs of focal interstitial and perivascular inflammatory reactions were evident following a course of three exposures to the enzyme. Interstitial pneumonia with characteristic generalized vasculitis and perivasculitis was produced following seven or nine inoculations. An enzymatically inactive preparation of enzyme 1, even by repeated administration, proved ineffective in eliciting pneumonia. Intracellular antigen within macrophages/histiocytes was demonstrated in the lungs of all experimental animals, including those which had been exposed to inhibited enzyme. Repeated exposure to the enzymatically active preparation resulted in the deposition of immunoglobulin and complement in association with vascular endothelia and in the walls of small- and medium- sized blood vessels; both immunoglobulin and complement could also he demonstrated within macrophages/histiocytes. On the basis of these findings it is concluded that (1) Farmer's lung- like interstitial pneumonia may be produced in rabbits by exposure to a purified, enzymatically active derivative of M. facni, (2) an important pathogenic principle of the disease may consist in the rapid vascular deposition of immune complexes (type III reaction), and (3) damage by direct enzyme action may prove to contribute significantly in eliciting tissue damage by (an) ancillary mechanism(s) not yet understood. [ABSTRACT FROM AUTHOR]