The regional cerebral metabolic rate for glucose was measured with the [(14)C2deoxy-D-glucose technique in young and aged male Fischer-344 rats, following administration of cholinergic (arecoline) dopaminergic (haloperidol, bromocriptine), and serotonergic (m-chlorophenylpiperazine) drugs. For arecoline, the absence of age differences in most brain areas indicated that muscarinic receptor mechanisms are intact in the senescent rat brain. Responses to bromocriptine and haloperidol were reduced in senescent as compared to younger rats, suggesting reduced central dopaminergic function, and an imbalance between cholinergic and dopaminergic systems. Aged rats displayed reduced responsivity to m-chlorophenylpiperazine, indicating an age-dependent functional defect in serotonergic neurotransmission. A model of cholinergic cortical deafferentation was implemented in rats, lesioning the nucleus basalis magnocellularis. Initial cerebral metabolic deficits returned to normal within two weeks after lesioning in young rats.