Interest in identifying brain areas mediating the behavioural effects of nicotine led to autoradiographic studies on the distribution of cerebral metabolic responses to nicotine. The 2-deoxy-D-[1-14C] glucose method was used to map and quantitate nicotine's effects in the rat brain. The method allows simultaneous measurement of the regional cerebral metabolic rate(s) for glucose (rCMRglc), an index of functional activity, throughout the central nervous system. It provides information about sites of initial drug interactions, and of secondary effects propagated via afferents to remote areas. In rats given acute systemic (-)nicotine, stimulation occurs in brain areas which contain specific binding sites for [3H] nicotine, indicating that the sites are true receptors, linked to functional activity. Doses of nicotine that are discriminated by rats and that produce behavioural and physiological effects stimulate rCMRglc. The stimulation is transient and is antagonized by mecamylamine. Affected areas include limbic structures, components of the visual system, brainstem nuclei important in cardiovascular reflexes, and areas involved in motor function. The distribution of nicotine's in vivo effects on rCMRglc implicates various brain regions in the behavioural and physiological effects of nicotine. Future studies employing positron emission tomography will assess relations between nicotine's effects on mood and rCMRglc in man.