There is evidence that glucocorticoids mediate the activity of mesencephalic dopaminergic neurons which play an important role in drug-seeking behaviour and that the absence or presence of glucocorticoids determines the intensity of drug self-administration. Moreover, some experiments indicate that corticoids are increased after substance induced dopaminergic stimulation. These findings could imply (a) that differences in basal glucocorticoid levels are associated with differences in craving or (b) that dopamine (DA) induced corticoid release is an indicator of the sensitivity of the dopaminergic system. Therefore, in a sample of 36 male smokers whose DA system was challenged by a DA agonist (lisuride = LIS) and a DA antagonist (fluphenazine = FLU) in a balanced placebo controlled double-blind crossover design, it was investigated if (a) basal cortisol differences,and (b) drug induced cortisol responses are related to the amount of nicotine craving after 3.5 h of deprivation from smoking. There were no differences in craving between subjects with high and low basal cortisol levels irrespective of the pharmacological treatment. However, the size of the cortisol change after the DA challenge and deprivation emerged as a good predictor for the amount of craving in that drug condition in which the cortisol response was most pronounced. Findings were interpreted as evidence for the role of cortisol as an indicator of DA sensitivity. Copyright (C) 2003 John Wiley Sons, Ltd.