Silver nanoparticles (AgNPs) have found a variety of uses including biomedical materials; however, studies of the cytotoxicity of AgNPs by size effects are only in the beginning stage. In this study, we examined the size-dependent cellular toxicity of AgNPs using three different characteristic sizes (∼ 10, 50, and 100 nm) against several cell lines including MC3T3-E1 and PC12. The cytotoxic effect determined based on the cell viability, intracellular reactive oxygen species generation, lactate dehydrogenase release, ultrastructural changes in cell morphology, and upregulation of stress-related genes (ho-1 and MMP-3) was fairly size- and dose-dependent. In particular, AgNPs stimulated apoptosis in the MC3T3-E1 cells, but induced necrotic cell death in the PC12 cells. Furthermore, the smallest sized AgNPs (10 nm size) had a greater ability to induce apoptosis in the MC3T3-E1 cells than the other sized AgNPs (50 and 100 nm). These data suggest that the AgNPs-induced cytotoxic effects against tissue cells are particle size-dependent, and thus, the particle size needs careful consideration in the design of the nanoparticles for biomedical uses. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2012.