Abstract: The kappa (κ) opioid system appears to interact with nicotine in the modulation of locomotion and addiction related processes. In this study we have investigated the possible implication of the κ-opioid system in the effects of nicotine on anxiety and adrenocortical activity. In two different experiments, we analysed the possible interaction between nicotine (0.5mg/kg i.p.) and either the κ-opioid receptor antagonist nor-binaltorphimine (5mg/kg i.p.) or the κ-opioid receptor agonist U50,488H (1mg/kg s.c.). Behavioural and endocrine experiments were performed in different groups of animals. Animals were exposed to the holeboard immediately followed by the plus-maze. Serum corticosterone levels were determined by radioimmunoassay. Nicotine induced an anxiogenic-like effect in the plus-maze and a significant decrease of holeboard activity. The anxiogenic-like effect in the plus-maze was not modified by any of the κ-opioid receptor ligands. Nicotine also induced a significant increase in the corticosterone levels, and the κ antagonist, which did not exert any effect per se, antagonised this effect. The κ-agonist U50,488H induced a significant increase in corticosterone concentration when administered alone. We provide the first evidence for the involvement of the κ-opioid receptor in the stimulatory effect of nicotine on adrenocortical activity. [Copyright &y& Elsevier]