Fish exposure to environmental stressors (e.g. chemicals, hypoxia, temperature) induce responses enabling them to cope with alterations in their environment. A stress response involves a wide array of changes, from molecular to physiological and behavioural, set to counteract the effect of the stressor and recover homeostatic equilibrium. Among other processes, there is activation of the hypothalamus-pituitary-interrenal (HPI) axis, resulting in stimulation of the steroidogenic pathway and release of cortisol, important mediator of the adaptive response to stress. The purpose of this study was to evaluate if exposure of a marine teleost (gilthead sea bream) to gold nanopartides (AuNP) could interfere with the HPI axis eliciting an acute stress response and how this response would be linked with alterations in the mRNA levels of target genes in the head kidney, important centre of endocrine response in fish. Fish were exposed via water, for 96 h, to four concentrations (0, as control, 4, 80 and 1600 mu g.L-1) of 40 nm spherical AuNP, covered with two different types of coatings (citrate and PVP). At the end of the exposure, fish were anesthetized and blood and the head kidney sampled. Results showed that exposure to 1600 mu g.L-1 AuNP-citrate and 80 mu g.L-1 AuNP-PVP increased plasma cortisol levels, compared to controls, but caused no change in glucose levels. AuNP modulated the expression of target genes related to oxidative stress, cell-tissue repair, immune function and apoptosis in the head kidney of fish. The patterns of response were distinct for the two coatings tested. Unlike AuNP-citrate, AuNP-PVP elicited an inverted U-shaped response. Present findings demonstrated that AuNP were able to activate the fish HPI axis and alter a battery of related molecular markers in the head kidney. (C) 2017 Elsevier B.V. All rights reserved.