Compared to other drugs of abuse, studies of the effects of nicotine on intracranial self-stimulation (ICSS) are few in number. Since the effect of nicotine on reward is not well established, one goal of the present study was to clarify the characteristics of nicotine-induced changes in brain stimulation reward using a rigorously validated, rate-free and reward-selective procedure. Once established, the second goal was to assess the ability of specific dopamine (sulpiride), serotonin (MDL 26,508), and mixed dopamine/serotonin (MDL 28,133A) antagonists to modify nicotine's effects.