Chronic infusion of nicotine has been shown to result (1) in an increase in nicotine binding sites in the brain and (2) in a distinct pattern of increases in local cerebral metabolic rate for glucose (CMRglc). The present study addresses two questions: (1) whether a one-day withdrawal of nicotine after a two-week exposure is long enough to restore local CMRglc to the preinfusion values and (2) whether an acute nicotine infusion after one day's withdrawal would influence local CMRglc. Chronic infusion of L-nicotine (12.5 micrograms/kg/min) was performed by osmotic minipumps. Local CMRglc was measured using the quantitative 2-deoxyglucose method in conscious rats. The following results were obtained: (1) a one-day withdrawal of nicotine after a two-week chronic infusion restores local CMRglc to a pattern which is close to the control pattern obtained without any nicotine infusion, and (2) an acute infusion of nicotine after a one-day withdrawal of a chronic nicotine infusion induces distinct increases in local CMRglc of several brain structures; these are essentially identical with structures which are activated during an acute nicotine infusion in otherwise untreated rats (no chronic infusion). The data indicate: (1) The main effects of chronic nicotine infusion on local CMRglc have disappeared after one day of nicotine withdrawal. (2) An acute load of nicotine in such nicotine-withdrawal rats has effects on local CMRglc which resemble those found in previously untreated rats during an acute nicotine infusion. (3) In contrast to most binding studies which have shown persisting increases in nicotine binding sites after one day's withdrawal of chronic nicotine, local CMRglc is restored to control values and can be again activated by an acute nicotine infusion.