Pathologic changes, brought about either by inoculation of murine sarcoma virus (Moloney) or by injection of virus-induced tumor tissue, were studied in 204 mice from experiments described in this Journal (40: 1101–1112, 1968). The common lesion at the site of subcutaneous or intramuscular inoculation was composed of mixtures of inflammatory cells and granulation tissue that permeated subcutaneous tissues and muscle. With time, these lesions became organized, irregular masses of indurated granulomatous tissue. This tissue consistently contained atypical mesenchymal cells of a type and size not observed in the usual reaction to injury. The atypical cells were large, often multinucleate, and often had distinctly prominent perinuclear concentrations of cytoplasmic material. Although these cells had characteristics of neoplastic cells, the predominant inflammatory component of the lesions better fitted the designation “atypical granuloma”—a term that connotes the complex structure of the lesions as well as their biologic behavior. Lesions of similar type were frequently observed in the spleen, adrenal glands, liver, internal genitalia, peritoneal surfaces, and retroperitoneal areolar tissues. Although these lesions distant from the site of injection contained scattered atypical and presumably neoplastic mesenchymal cells, their distribution suggested they resulted from dissemination of virus rather than dissemination of neoplastic cells. Some lesions persisted for long periods or recurred at sites of injection. These showed a wide range of response from persistent granulomatous inflammation to inert scarring. Tumors with all morphologic characteristics of either mesenchymal cell sarcomas or hemangiosarcomas seemed to evolve from a small percentage of the granulomas. In many ways, the reaction to the murine sarcoma viruses merits comparison and consideration as a model for the study of the reticuloendothelioses of man.