Tissue injury was studied in rat lung and in the dermal vasculature after the injection of preformed, heterologous immune complexes. In lung, these complexes induced an acute, hemorrhagic alveolitis with large numbers of neutrophils. There were marked increases in permeability and extensive intrapulmonary hemorrhage. Similar changes of lesser magnitude developed at sites of dermal injection of immune complexes. The lung and skin reactions were complement- and neutrophil-dependent. The tissue damage in lung, as measured by permeability changes and development of hemorrhage, appeared to intensify during the first 24 hours and then began to wane. By the second and third day after the acute insult, permeability changes and hemorrhage had returned toward control values. Inflammatory, tissue-damaging reactions did not develop in lung or dermis if heat-aggregated bovine serum albumin was injected in place of immune complexes. This model permits the direct study of lung and vascular injury induced by preformed immune complexes.