Mouse IgG and IgA, with reactivity to dinitrophenol conjugated to carrier protein, have been isolated from myeloma proteins by means of a variety of affinity techniques. The IgA was predominantly in the dimeric form. The in vitro and in vivo biological activities of IgA-containing immune complexes were assessed in the rat. IgA-containing immune complexes were demonstrated, in a dose-dependent manner in vitro, to activate neutrophils and to generate O.-2. In addition, these immune complexes showed evidence of complement activation in vitro, by the use of immunofixation techniques. When IgA was instilled into the airways of rats and antigen was injected intravenously, acute lung injury occurred, as reflected by increases in lung permeability and morphological changes consisting of blebbing of endothelial cells, intra-alveolar hemorrhage, and fibrin deposition. The lung changes were directly proportional to the amount of IgA instilled into the airways and failed to occur if intravenous injection of antigen was omitted. Lung injury did not occur in animals that received an intravenous injection of antigen in the absence of an airway injection of IgA. Lung injury related to IgA-containing immune complexes was complement dependent but neutrophil independent. In companion studies with mouse IgG-containing immune complexes, acute lung injury also occurred and had morphological features similar to those associated with IgA-induced lung injury except that, in the case of IgG immune complex-induced damage, neutrophils were more evident. Acute lung injury induced by IgG-containing immune complexes, whether of mouse or rabbit origin, was complement and neutrophil dependent. The similarities and differences between IgG- and IgA-associated acute immune complex-induced injury of rat lung were reinforced by the use of morphometry techniques. Studies with another monoclonal IgA antibody-containing antigen-binding activity to phosphorylcholine also demonstrated the ability of IgA antibody to cause acute lung injury in the rat. Neither antibody alone nor antigen (phosphorylcholine linked to bovine serum albumin) alone produced evidence of lung injury. These studies indicate for the first time that immune complexes containing IgA have lung-damaging properties and that the pathogenic mechanisms are different from those associated with IgG-associated immune complex-induced acute lung injury.