Daily inhalation by mice of an environmental irritant (H 2SO 4) followed by consequent respiratory immunization with a particulate antigen (sheep red blood cells, SRBC) induced severe interstitial pneumonitis. Inhalation of H 2SO 4 per se resulted in accumulation of i.v. injected globulin in the lungs of mice, without significant change in lung weight. In addition, when marker colloidal carbon particles were injected i.v. following H 2SO 4 inhalation, the carbon was rapidly trapped in the capillary wall in the lungs. Homologous anti-SRBC serum instilled into the respiratory tract followed by subsequent SRBC inhalation produced inflammation and injury similar to that generated by H 2SO 4 in combination with particulate antigen. It is postulated that following irritant inhalation, the permeability of alveolocapillary membranes increases, so that immune complexes formed by pre-existing circulating antibodies and inhaled antigen can initiate subsequent lung injury.