The effect of age on phosphate incorporation into phosphatidylinositol 4-phosphate (PIP), phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidic acid (PA) was studied. Lysed crude synaptosomal fractions of different brain regions of 3-month-old and 32-month-old Brown Norway rats were used. The brain regions tested were the hippocampus, frontal cortex, occipital/parietal cortex, entorhinal/pyriformal cortex, striatum/septum, thalamus and hypothalamus. The individual specific phosphorylating activities were unevenly distributed within the brain of Brown Norway rats. Strikingly, the distribution of phosphate incorporation into PIP2 was opposite from that of phosphate incorporation into PA. Phosphate incorporation into PA decreased (− 15%) with age in almost all brain regions tested, whereas phosphate incorporation into PIP2 decreased with age only in the frontal cortex (− 20%) and in the hypothalamus (− 8%). The effects of age may reflect a deterioration of phosphoinositide metabolism, with its function in signal transduction coupled to receptors via G-proteins, in the brain regions involved. In addition, there was an age related decrease in protein content and total phospholipid phosphorus content of lysed crude synaptosomal preparations of all brain regions. The high correlation between the changes in these parameters may be indicative of a decrease in the number of size of synaptosomes with age in the brain regions involved.