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Abstract: The antibacterial properties of silver nanoparticles (AgNPs) are widely exploited in a variety of medical and consumer products. AgNPs in these products can be released into the aquatic environment, however, the potential toxicity of AgNPs to organisms, including fish, is yet to be fully understood. The present study aimed to investigate the effects of the early life exposure to AgNPs on the hypothalamic–pituitary–interrenal (HPI) axis-mediated stress response in zebrafish (Danio rerio) larvae and adults. Zebrafish embryos were treated with AgNPs (0.5μg/mL) or Ag+ (0.05μg/mL) starting at 2h post fertilization (hpf). At 96hpf the larvae were either subjected to a swirling stress and euthanized, or raised to adulthood (10months) in silver-free water and then net-stressed, euthanized, and sampled. Whole-body basal or stress-induced cortisol levels in larvae were not affected by either AgNPs or Ag+; however, the transcript levels of corticotropin releasing factor (CRF), CRF-binding protein (CRF-BP), CRF-receptor 2 (CRF-R2), and pro-opiomelanocortin (POMCb) were significantly decreased by Ag+. The ability of the adult fish to release cortisol in response to a stressor was also not affected, although the transcript levels of CRF, CRF-BP, and CRF-R1 in the telencephalon were differentially affected in fish exposed to Ag+ as embryos. This is the first study that investigated the potential endocrine-disrupting effects of AgNPs during the early life stages and although AgNPs or Ag+ did not affect the ability of zebrafish to elevate cortisol levels in response to a stressor, the effects on transcript levels by Ag+ should be investigated further since CRF does not solely regulate the HPI axis but is also implicated in other physiological processes. [Copyright &y& Elsevier]