A B S T R A C T Lower respiratory tract and systemic cell-mediated immunity have been studied in rabbits after infection with Listeria, monocytogenes or Diplococcus pneumoniae. Respiratory tract cell-mediated immunity was evaluated by direct and indirect assays of migration inhibitory factor (MIF) production. Systemic delayed hypersensitivity was determined by means of intradermal testing with appropriate antigens.Aerosol exposure to listeria was followed by markedly increased numbers of free lower respiratory tract cells. These cells manifested antigen-stimulated inhibition of migration (mean inhibition of migration = 30.4%). Pneumococcal pneumonia was associated with similar but less dramatic changes. Intravenous administration of organisms was uncommonly followed by inhibition of lower respiratory tract cells in direct migration assays.Fractionated MIF, as well as crude supernates of antigen-stimulated lower respiratory tract and lymph node lymphocytes from animals exposed to listeria aerosols, caused inhibition of normal alveolar macrophage migration. MIF, produced by lymph node lymphocytes, has a molecular weight of approximately 65,000 and is inactivated by chymotrypsin or neuraminidase.Delayed dermal hypersensitivity to listeria antigen was observed in 54 of 55 animals exposed to listeria aerosols and in all 9 animals infected by the intravenous route. Delayed dermal reactions to pneumococcal sonicate antigen (but not capsular polysaccharide) fol-