Polymorphonuclear leukocytes from dogs, humans, and rabbits, and dog alveolar macrophages and dog mononuclear leukocytes were investigated for their ability to induce experimental emphysema in the dog. Eighteen dogs were treated with aerosolized homogenates of the various cell types or control substances. In decreasing order, the emphysema-inducing ability of the different cell homogenates was dog polymorphonuclear leukocytes, human polymorphonuclear leukocytes, dog alveolar macrophages, rabbit polymorphonuclear leukocytes, and dog mononuclear leukocytes. The last 2 cell types produced little or no disease. Proteinase assays were performed on homogenates of all cell types. The ability of the cell homogenates to induce experimental emphysema correlated with the presence of in vitro neutral and alkaline protease activity.