To clarify the pathogenesis of respiratory disease induced by drug allergy, an animal model of eosinophilic lung disease induced by drug was developed. Administration of an aerosol of piperacillin (PIPC) to guinea pigs immunized with emulsion of PIPC and complete Freund's adjuvant (CFA) produced diffuse interstitial lung disease with alveolar wall thickening and alveolitis characterized by marked increase in eosinophils and mononuclear cells. A significant increase of eosinophils in bronchoalveolar lavage fluid was shown in PIPC＋CFA-sensitized animals compared with that in non-sensitized, PIPC-sensitized and CFA-sensitized animals. Using lymphocytes from BAL fluid, drug lymphocyte stimulation test (DLST) revealed a higher stimulation index (S. I.) than that using lymphocytes from peripheral blood tn 5 of seven animals. These findings suggest that eosinophils and lymphocytes (especially lymphocytes sensitized by antigen) play important roles in drug-induced respiratory disease. Furthermore, it is considered that lung lymphocytes were more active than lymphocytes in peripheral blood in the experiment, and local lymphocytes in BAL contributed to the pathogenesis of the respiratory disease induced by drug allergy.