Hippocampal and entorhinal cortex glucose metabolism were studied by C-14-2-deoxyglucose (2-DG) autoradiography in anesthetized rats with and without continuous theta rhythm (theta). 2-Deoxyglucose changes in specific cytoarchitectonic regions were precisely assessed by an innovative approach. In the absence of theta there were areas with a higher glucose metabolism corresponding to neuropile regions at CA3, dentate gyrus, and subiculum, while the cellular layers always showed lower values. In the presence of theta, provoked by intraventricular injections of anticholinesterases (i.e., physostigmine) or curarimimetics (i.e., d-tubocurarine), 2-DG uptake showed two opposite significant changes in relation to controls: a) it increased in the outer zone of the molecular layer (inner blade) of the dentate gyrus, and in the stratum lacunosum-moleculare of CA3, suggesting an increase in perforant path input during theta rhythm; b) it decreased in the hilar dentate region. This noteworthy decrease in metabolic activity probably reflects an hilar inhibition by local circuits during theta rhythm generation.