Local cerebral glucose utilization (LCGU) was measured in 45 regions of the rat brain during chronic nicotine infusion using the quantitative autoradiographic 2-deoxy-D-[1-14C]glucose method described by Sokoloff et al. [J. Neurochem., 28 (1977) 897-916]. Osmotic minipumps, filled with L-nicotine, were implanted 14 days before the measurement of LCGU. The infused nicotine dose of 12.5 micrograms/kg/min resulted in a plasma nicotine concentration of 77 +/- 17 and a plasma cotinine concentration of 504 +/- 137 (mean +/- S.E.M.) ng/ml plasma. One day before the LCGU experiment was performed, spontaneous locomotor activity was measured and found to be reduced significantly. Measurement of LCGU showed a significant increase in 6 of the 45 brain structures examined, i.e. globus pallidus, septal nucleus, lateral geniculate body, superior colliculus (superficial grey layer), interpeduncular nucleus and optic chiasm. These results are partly congruent with previous data of our group obtained during acute nicotine infusion, insofar as LCGU was increased in the optic chiasm, the lateral geniculate body, the superior colliculus, and the interpeduncular nucleus. On the other hand, the increased LCGU in the globus pallidus and septal nucleus occurred during chronic infusion only; other structures were not affected by chronic infusion although their LCGU had been raised during acute infusion. It is concluded that chronic nicotine infusion has distinct effects on the functional activity of several brain structures which are partly congruent with those affected during acute nicotine infusion and partly divergent from them.