Engineered nanoparticles (NPs) can potentially generate adverse effects at the tissue, organ, cellular, subcellular, DNA, and protein levels due to their unique physico-chemical properties. Dissoluble NPs (e.g. nZnO) can be toxic in aquatic organisms. We compared effects of nZnO and corresponding concentrations of released Zn(II) by water-soluble ZnCl2 on larval zebrafish Danio rerio (72 h post fertilization) by analyzing changes in expression levels of stress-related genes (p53, rad51, mt2) by qRT-PCR. Additionally, genotoxicity of nZnO and Zn(II) was assessed. The lethal concentrations for 50% mortality (LC50) in larval zebrafish exposed for 96 h to 0 to 70 mg l(-1) nZnO and Zn(II) were 21.37 +/- 1.81 mg l(-1) (95% CI) and 4.66 +/- 0.11 mg l(-1), respectively. A concentration-dependent increase in DNA strand breaks was detected in cells from larvae exposed (96 h) to nZnO and Zn(II). DNA damage was higher in Zn(II)-than nZnO-exposed larvae. Induction of stress-related genes in larvae was complex and was not directly related to nZnO and Zn(II) concentrations, although there was significant induction in the mt2 gene of larvae exposed to Zn(II) and nZnO relative to controls. mt2 induction of 20.5 +/- 1.9-fold and 2.5 +/- 0.8 fold change (mean +/- SEM) was observed in larvae at the highest Zn(II) and nZnO concentrations (3 and 6 mg l(-1)), respectively. The results suggest that toxicity associated with nZnO is primarily due to the release of Zn(II).