One important neuroendocrine action of nicotine in the male rat is an increase in the secretion of corticosterone which is seen upon acute and acute intermittent exposure to nicotine. Tolerance develops to this action of nicotine upon chronic exposure, and in the withdrawal phase serum corticosterone levels are substantially reduced. In contrast, no significant increases of serum corticosterone levels were observed upon acute intermittent treatment with nicotine in the dioestrous rat. Available evidence indicates that corticosterone can modulate dopamine transmission in the basal ganglia via glucocorticoid receptors within the nucleus accumbens and neostriatum, and via glucocorticoid receptor immunoreactivity in nigrostriatal and mesolimbic dopamine pathways. Through concerted pre- and postsynaptic actions glucocorticoids may decrease dopamine transmission, especially that mediated by D2 receptors in these regions. In view of the hypothesis that the mesolimbic dopamine pathways mediate the euphoric effects of nicotine, the secretion of corticosterone induced by nicotine in the smoking male may substantially influence the mood elevating activity of nicotine. Thus, individual smoking habits may depend on the ability of nicotine to induce corticosterone secretion, which obviously would also vary with the degree of stress. The glucocorticoids may in a similar way influence the arousal action of nicotine because of the high number of glucocorticoid receptors present both in noradrenaline cell bodies of the locus ceruleus and within the entire cerebral cortex.