Adrenocorticotrophic hormone (ACTH) and structural analogs of the fragment ACTH4-9 have marked effects upon behavior (particularly in relation to memory processes). The effects of the chronic (10 day) administration of the potent analog (Met(O2)4,D-Lys8,Phe9]ACTH4-9(100 microgram/kg per day i.p,) upon local cerebral glucose utilization have been examined using the autoradiographic 2-deoxyglucose technique in the attempt to identify the neuroanatomical sites involved functionally in the central actions of this ACTH4-9 analog. Of the 49 anatomically discrete regions examined, significant increases in glucose utilization were observed only in the hippocampus (stratum molecular lacunosum lacunosum and parasubiculum, increased by 16 and 17% respectively), the anterior nucleus of the thalamus (by 23%) and anterior cingulate cortex (by 30%). The highly localized alterations in glucose utilization which were observed following treatment with this ACTH4-9 analog provide evidence for the functional involvement of a hippocampal-anterior-thalamic-anterior cingulate cortical circuit in the actions of this peptide fragment.