Desmin is a smooth muscle protein consisting of intermediate filaments. It is also present in other cell types. We obtained desmin antibodies from New Zealand white rabbits which were immunized with desmin following its extraction from chicken gizzard smooth muscle. By immunocytochemical methods, the antibody stained the Z-line of rat skeletal myofibrils and produced only one band with chicken gizzard desmin by immunoblotting. The antibody was specific for desmin, but was not tissue-specific. Wistar rat liver was studied by indirect immunoperoxidase and immunofluorescent methods using the antibody. Cells which reacted were diffusely distributed in the hepatic lobule, had stellate shape, bore elongated cytoplasmic extensions and contained few fat droplets. The fat droplets increased in size and amount after administration of vitamin A, and contained vitamin A as determined by ultraviolet exposure and gold impregnation. The fat-containing cells did not phagocytose carbon particles after injection of colloidal carbon and were, therefore, classified as fat-storing cells (Ito cells).