To assess the toxicity of copper nanoparticles (23.5 nm) in vivo, LD(50), morphological changes, pathological examinations and blood biochemical indexes of experimental mice are studied comparatively with micro-copper particles (17 microm) and cupric ions (CuCl(2).2H(2)O). The LD(50) for the nano-, micro-copper particles and cupric ions exposed to mice via oral gavage are 413, >5000 and 110 mg/kg body weight, respectively. The toxicity classes of nano and ionic copper particles both are class 3 (moderately toxic), and micro-copper is class 5 (practically non-toxic) of Hodge and Sterner Scale. Kidney, liver and spleen are found to be target organs of nano-copper particles. Nanoparticles induce gravely toxicological effects and heavy injuries on kidney, liver and spleen of experimental mice, but micro-copper particles do not, on mass basis. Results indicate a gender dependent feature of nanotoxicity. Several factors such as huge specific surface area, ultrahigh reactivity, exceeding consumption of H(+), etc. that likely cause the grave nanotoxicity observed in vivo are discussed.