Mechanisms of inflammation in the lung will be studied as they occur in response to inhaled mitogenic and antigenic substances. In previous work we have shown that T-cell mitogens (concanavalin A, phytohemagglutinin) induced a diffuse interstitial inflammation when inhaled by unsensitized rabbits. Animals possessing high titers of antibody, on the other hand, manifest only minimal injury following aerosol challenge with specific antigen, but develop devastating inflammatory reactions following challenge with antigen plus mitogen. Immunohistochemical staining has demonstrated localization of antigen, specific antibody and C3 in these severely injured lung tissues. We propose that mitogen-induced pulmonary injury is mediated by lymphokines released from T-cells stimulated within the lung, and thus serves as a useful model for cell-mediated pulmonary disease. We further hypothesize that such cell-mediated injury serves as a critical "trigger" to initiate immune complex formation between inhaled antigen and humoral antibody. We wish to test these hypotheses by (1) relating Con A-induced interstitial pneumonitis with local lymphokine release; (2) demonstrating the ability of lymphokines prepared in vitro to induce pulmonary injury directly; (3) defining the role of cell-mediated reactions in initiating local immune complex injury; (4) further defining the ability of cyclic nucleotides to modulate inflammatory lung disease; and (5) characterizing mitogens derived from Micropolyspora faeni and testing them for their ability to initiate immune complex injury in experimental animals.