There is increasing evidence that the rewarding effect of nicotine is mediated by the mesolimbic dopamine system. The first objective of this study was to examine the dopamine response to repeated i.v. infusions of nicotine. Using in vivo microdialysis in awake and freely moving male Sprague-Dawley rats, we demonstrated that i.v. nicotine infusions (0.16 mg/kg or 0.32 mg/kg per infusion) produced increases in extracellular dopamine levels that were dose- and infusion order-dependent. Acute tolerance was evidenced by the smaller dopamine response produced by a second infusion of nicotine, administered 1 h after the first one. Tolerance was reversible, since the dopamine response to a second infusion of nicotine was unchanged when the interval between the infusions was increased to 3 h. Ibogaine, an alkaloid found in Tabernanthe iboga, is claimed to decrease smoking and to have an anti-nicotinic action. The second objective of this study was to establish whether this claim has any neurochemical basis. Pretreatment with ibogaine (40 mg/kg, i.p.) 19 h prior to the first nicotine infusion (0.32 mg/kg per infusion) significantly attenuated the increase in extracellular dopamine levels induced by-the nicotine infusions, suggesting that ibogaine may decrease the rewarding effect of nicotine.