Two cases of actinic granuloma are described with emphasis on distinctive clinical and histopathologic features, including immunoperoxidase staining for lysozyme and immunophenotyping of mononuclear leukocytes. Actinic granuloma presents in chronically sun-damaged skin as normally colored to erythematous papules that coalesce to form centrifugally enlarging annular patterns. By light microscopy, a granulomatous infiltrate of giant cells and histiocytes is seen to be intimately related to the presence of elastotic fibers in the upper dermis. Selective localization of lysozyme in the giant cells of the granuloma is apparent by a tertiary antibody immunoperoxidase technique. Determination of mononuclear leukocyte subsets with monoclonal antibodies reveals a predominance of helper T cells in the lymphocytic infiltrate associated with the granuloma. It is postulated that actinic granuloma represents a cell-mediated immune response to weakly antigenic determinants on actinically altered elastotic fibers.