[3H]Inositol 1,4,5-trisphosphate [( 3H]Ins-(1,4,5)P3) binding studies were done on the human brain obtained at autopsy. The specific [3H]Ins(1,3,4,5)P3 binding sites in the cerebral and cerebellar cortices consisted of a single component with a high affinity (Kd = 11.3 and 16.5 nM, Bmax = 0.8 and 6.4 pmol/mg protein, respectively). The binding of [3H]Ins(1,4,5)P3 was potently inhibited by Ins(1,4,5)P3, in a nanomolar concentration, while other inositol phosphates and inositol were either much less potent or did not inhibit binding. The binding sites for [3H]Ins(1,4,5)P3 were discretely localized and were in the order: cerebellum much greater than basal ganglia, cerebral cortex greater than rhinencephalon greater than diencephalon, mesencephalon. There was an age-related loss of [3H]Ins(1,4,5)P3 binding in the frontal cortex. In the brains of patients with Parkinson's disease, [3H]Ins(1,4,5)P3 binding sites were reduced by about 50% in the caudate nucleus, putamen, and pallidum, while there were no differences in the frontal cortex, as compared to findings in the age-matched controls. Our findings suggest that [3H]Ins(1,4,5)P3 binding sites are closely linked to neural elements in the human brain.