BACKGROUND: Academic stress is a good model of psychological stress in humans and is thus useful for studying psychoneurohormonal changes. The aim of the current study was to examine the effect of academic examination stress on activation of the hypothalamus-autonomic nervous system (HANS) and the hypothalamic-pituitary-adrenocortical (HPA) axis, through the measurements of changes in neuro-hormones during final exams as compared to the pre-exam baseline. MATERIALS AND METHODS: Forty-eight first- and second-year female medical students participated. Plasma leptin, neuropeptide Y (NPY), nitrite, nitrate, andrenomedullin, cortisol and adrenocorticotropic hormone (ACTH) were measured at baseline and during final examinations. RESULTS: Plasma levels of cortisol, ACTH, NPY, adrenomedullin, nitrite and nitrate increased during times of academic stress as compared to baseline levels. However, only plasma leptin level was decreased during the academic stress as compared to baseline, probably through a negative feedback mechanism resulting from sympathetic stimulation. The results indicate that both the HANS and HPA are involved in this type of stress and both are activated at the same time. CONCLUSION: Academic stress induced significant neurohormonal changes. Leptin, NPY, nitrite, nitrate, adrenomedullin, cortisol and ACTH can be considered part of a complex mosaic model of the neuroendocrine system during academic stress.