Silver nanoparticles (AgNPs) are present in a multitude of consumer and medical products; however, the toxicity of AgNPs is not fully understood. This research aimed to elucidate the relationship between AgNP cytotoxicity and oxidative stress and damage in rainbow trout (Oncorhynchus mykiss) hepatocytes and erythrocytes in comparison to silver ions (Ag(+)). Generally the cytotoxicity of AgNPs and Ag(+) was similar, such that both silver types generated reactive oxygen species, decreased glutathione levels, and decreased activities of glutathione reductase and glutathione-S-transferase. Nonetheless, the two silver types had different cellular targets; AgNPs increased lipid peroxidation without apparent uptake into the cells whereas Ag(+) increased DNA damage. Furthermore, the toxicity of both silver types was generally decreased in cells treated with cysteine while treatment with buthionine sulfoximine increased the toxicity of both silver types.