The local immunopathological response was analyzed in six patients who had a revision of a total hip prosthesis because of an aggressive granulomatous lesion and in six patients who had a revision because of common loosening of the prosthetic stem. All twelve patients had had a total replacement arthroplasty for primary osteoarthrosis. All of the prostheses had been cemented. The aggressive granulomas consisted of well organized connective tissue containing histiocytic-monocytic and fibroblastic reactive zones. The granulomas were highly vascularized, and villous structures were observed at many sites. In contrast, the areas around the loose cemented stems were characterized by dense connective tissue. Immunohistological evaluation revealed that most of the cells in the aggressive granulomatous tissue were multinucleated giant cells and C3bi-receptor and nonspecific esterase-positive monocyte-macrophages. This cytological finding suggests a foreign-body-type reaction, compatible with the rapidly progressive lytic nature of the lesion that was shown radiographically. There was a clear-cut difference between aggressive granulomatosis and the more common lesion accompanying prosthetic loosening--namely, the relative lack of activated fibroblasts in granulomatosis. We suggest that granulomatosis involves an uncoupling of the normal sequence of monocyte-macrophage-mediated clearance of foreign material and tissue debris that is normally followed by fibroblast-mediated synthesis and remodeling of the extracellular matrix. We also suggest that aggressive granulomatosis in association with a cemented hip prosthesis is a distinct entity, not only clinically and radiographically, but also histopathologically.