After unilateral destruction of the nucleus basalis magnocellularis (NBM) in 3-month-old rats, which reduces cholinergic inputs to the ipsilateral frontoparietal neocortex, regional cerebral metabolic rates for glucose (rCMRglc) of denervated cortex are initially reduced, but nearly normalize by 2 weeks. To examine functional reorganization of the brain after unilateral destruction of the NBM, a correlation analysis of rCMRglc was performed on two groups of 16 young rats 2 weeks after stereotaxic ablation of the right NBM with ibotenate or sham surgery. rCMRglc was measured in 117 brain regions of awake rats with the [14C]deoxyglucose method. For each region pair, a partial correlation coefficient was calculated for rCMRglc across animals. Most correlations between cholinergic nuclei of both left and right forebrain (medial septum and diagonal band) and right (66/72, mean increase 0.44) but not left (39/72) frontoparietal cortical regions were larger (P < 0.001) in lesioned rats, as were those between most frontoparietal region pairs (516/630, P < 0.001). These results suggest that, after unilateral NBM ablation, (1) functional interactions are established between the remaining cholinergic forebrain and the deafferented cortex, (2) the neocortex becomes more integrated, and (3) functional reorganization involves both cortical hemispheres. These changes do not correspond to those reported to occur in Alzheimer's disease.