Phosphate-activated glutaminase (PAG) was assayed in homogenates of brain cerebellum, hippocampus or striatum from normal, starved for 48 h to 120 h or streptozotocin-diabetic rats. Only the hippocampal enzyme was increased (47%) by diabetes. Starvation had no effect in any of the regions studied. PAG of synaptosomes or of non-synaptosomal mitochondria from the hippocampus was also increased by 48% and 22% respectively in diabetes. PAG of synaptosomes from the cortex, the cerebellum, or the striatum or of the non-synaptosomal mitochondria from the cortex were not affected by diabetes or prolonged (120 h) starvation. A suggestion is presented that peripheral insulin, indirectly, may regulate PAG activity in a specific region of the rat brain.