The increased use of nano-sized metallic materials is likely to result in the release of these particles into the environment. It is, however, unclear if these materials are harmful to aquatic animals. Furthermore, because the dissolution of such nanomaterials will occur, it is probable that some of the adverse effects resulting will result from the dissolved metal species. In this study, therefore, we investigated the health and environmental impact of silver nanoparticles (Ag-NPs) on Japanese Medaka by studying changes in the expression of stress-related genes using real time RT-PCR analysis and compared these results with those of Medaka exposed to soluble silver ions. The stress-related genes selected here were metallothionein, HSP 70, GST, p53, CYP 1A and the transferrin gene. The expression levels of each gene were determined using two different Ag-NPs dosages and were quantified by measuring the mRNA concentrations in liver extracts with the Taqman-based Real-Time PCR method. The results suggest that these two silver forms have distinguishable toxic fingerprints between them. While the Ag-NPs led to cellular and DNA damage, as well as carcinogenic and oxidative stresses, genes related with metal detoxification/metabolism regulation and radical scavenging action were also induced. In contrast, the ionic silver led to an induction of inflammatory response and metallic detoxification processes in the liver of the exposed fish, but resulted in a lower overall stress response when compared with the Ag-NPs.