Immunologic mechanisms contribute to the pathogenesis of pulmonary disease by tissue damaging reactions of hypersensitivity. Therefore, we propose to study hypersensitivity reactions, i.e., immune complex disease and cell mediated hypersensitivity, elicited in the lungs of sensitized guinea pigs by aerosol or intratracheal challenge with specific antigen. We will determine the source of the reactants, e.g., antibodies and complement, involved in immune complex induced lung disease. Serum and lung lavage fluid from outbred guinea pigs with the pulmonary disorder will be analyzed qualitatively and quantitatively. Furthermore, the distribution of inhaled or intratracheally injected antigen and antibody complexed antigen will be evaluated in serum and lung lavage fluid by precipitation techniques, and in lung tissue by immunofluorescence and autoradiography. These studies will be performed in actively and passively (serum transfer) sensitized animals. We will study the role of sensitized lymphocytes in the mediation of experimental hypersensitivity pneumonitis. Lymphocytes obtained from the blood and lung lavage fluid of inbred guinea pigs with the pulmonary disorder will be tested for antigen induced migration inhibition factor production and blastogenesis. In addition, we will transfer lymphocytes from a sensitized donor to a normal recipient prior to challenge with aerosolized antigen.