There is evidence indicating that Ins 1,4,5-trisphosphate receptors (IP3R) are involved in the pathophysiology of abnormal brain function. A decreased number of IP3R in the brain of patients with Alzheimer's disease or olivopontocerebellar atrophy have been reported; however, the role of IP5R in the platelets of persons with these and other mental disorders has not been studied. We characterized IP3R in human platelet membranes by using [3H] inositol 1,4,5-trisphosphate ([3H]IP3) as the ligand. We observed a single, saturable binding site for [3H]IP3, which was time dependent and modulated by pH, inositol phosphates, and heparin. CaCl2 and cAMP, two important modulators of IP3R, altered [3H]IP3 binding to human platelet membranes. In the presence of EDTA, CaCl2 inhibited [3H]IP3 binding at lower concentrations, but stimulated [3H]lP3 binding at higher concentrations. In vitro addition of cAMP increased [3H]IP3 binding, whereas forskolin, which causes endogenous release of cAMP, inhibited the binding of [3H]IP3. These studies indicate that the pharmacologie properties of [3H]IP3 binding to human platelet membranes are similar to those of IP3R.