Functional activation in human brain produces an increase in glycolytic metabolism. Animal studies suggest activation-induced glycolysis is coupled to brain glycogenolysis. Medial forebrain bundle (MFB) stimulation activates the release of neurotransmitters which promote neocortical glycogenolysis in vitro. In the present study, active glycogen phosphorylase (GP), an index of glycogenolysis, is assessed histochemically in rat brain after 15 min of MFB self-stimulation. Active GP increased significantly in layers 4, 5b and 6 of granular neocortex ipsilateral to MFB self-stimulation. Restriction of increased glycogenolysis to granular neocortex suggests an important functional interaction between sensory neocortical processing and ascending MFB systems.