In a double-blind crossover design on 36 male smokers, differences in hormone responses to a serotonergic (citalopram) and dopaminergic (bromocriptine) challenge were tested, to compare transmitter responsivities in addicted and pleasure-motivated smokers with respective controls. A general score of smoking addiction, according to DSM IV criteria, was associated with a blunted prolactin decrease to bromocriptine, indicating a possible nicotine-induced desensitization of DA receptors. The single questionnaire-based symptom of tolerance was associated with a blunted cortisol response to citalopram, indicating a particular desensitization of serotonin receptors. Nontolerant but addicted subjects exhibited increased serotonergic responsivity, interpreted as resulting from low serotonin levels associated with lack of impulse control. The questionnaire-based score of pleasure-motivated (='indulgent') smoking was associated with high dopaminergic activity (pronounced prolactin responses), confirming findings obtained in subjects exhibiting reward-related personality factors.