Abstract Metals, such as Au, Ag, and Ni cause various types of allergic reactions. Several models have been proposed to explain the activation of metal-allergy, for example, analogous to typical haptens such as TNP, T cell recognize a complex of metal ions with MHC-embedded self-peptides. In general, metal-allergy means metal-ion allergy. On the other hand, with recent development of nanotechnology, nanomaterials (≤ 100 nm) including metal nanoparticles have been used in variety of fields, such as cosmetics and food. Due to their ultrafine size, nanoparticles have distinct property including their in vivo dynamics compared with both molecules and bulk particles. Here, we evaluated the sensitization potential of silver nanoparticles (nAg). The BALB/c mice were immunized with various size of nAg (10-100 nm) with LPS as adjuvant. One week after weekly immunization for 4 weeks, we challenged their immunized nAg on their ears and evaluated the ear swelling for 4 days. nAg with diameter of 10 nm, but not more than 10 nm, enhanced nAg-mediated ear swelling. Thus nAg less than 10 nm might have sensitization potential. Because nAg-immunization did not enhance Ag ion (Ag+)-mediated ear swelling, nAg-elicited immune responses did not have cross-reactivity to Ag+. Therefore, nAg-elicited immune responses were nAg-specific immune responses. We are now analyzing which cells and how the cells enable the specific recognition of nAg to reveal new perspective of acquired immune systems.