Vitronectin is a multifunctional glycoprotein known to be associated with the dermal elastic fiber network in human adults, with various types of human amyloid and with apoptotic keratin bodies in human skin. It has also been shown to bind to human keratin intermediate filaments and to intranuclear material in vitro. To learn more of its function and mode of tissue deposition, vitronectin in mouse skin was studied. Vitronectin was purified from mouse plasma and a polyclonal anti-vitronectin antiserum was produced. This was used in an avidin-biotin-peroxidase complex technique and in an immunofluorescence technique on biopsy sections of dorsal skin from mice. Hairless lightly pigmented mice, known to develop dermal amyloid deposits at advanced ages, were used, making it possible to study vitronectin's association not only with elastic fibers but also with amyloid. Association of vitronectin with elastotic material was investigated in mice exposed to ultraviolet radiation. No vitronectin immunoreactivity could be demonstrated in association with elastin-stained material in skin specimens from any of the mice, whether exposed to ultraviolet radiation or not. In contrast, vitronectin was constantly found to be associated with dermal amyloid deposits. Moreover, mouse vitronectin was found to bind to mouse keratinocytes when studied by immunofluorescence staining of skin sections that had been pre-incubated with mouse plasma as sources of vitronectin. The results indicate that vitronectin is associated with amyloid and can bind to intracellular structures in epidermal keratinocytes in mice as in humans, and that mouse tissue may be used for the study of vitronectin's interactions with amyloid and with intracellular structures.