Involutional lipoatrophy is an apparent idiopathic lipoatrophy with characteristic histopathologic features. We report a patient with a distant history of intramuscular injections and subsequent typical involutional lipoatrophy in whom macrophage invasion of the fat was prominent. Light microscopy revealed small, thin lobules of fat with focally prominent blood vessels and a variably hyaline background. Macrophages containing granular acid mucopolysaccharide material were present in direct apposition to lipocytes, around involuting lobules and between collagen fibers in the neighboring dermis. Focal deposits of iron were observed. Electron-microscopic examination revealed macrophages abutting lipocytes and containing lipid droplets, clear vacuoles and lysosomes in varying proportions. Lipocytes varied in size. The lipid appeared normal in most, but scattered cells contained electron-dense granules or needle-shaped clefts within the lipid. We speculate that previous injections in our patient stimulated a macrophage response, with subsequent regression of lipocytes of the neighboring fat lobules.