We ascertained platelet alpha 2-adrenergic receptor responsiveness in healthy young and elderly men and women by determining the minimum concentration of methylnorepinephrine, a selective alpha 2-adrenergic receptor agonist, required to initiate the primary and secondary aggregation response in platelet-rich plasma. We observed that platelets from elderly men required a smaller concentration of methylnorepinephrine to stimulate primary aggregation than did platelets obtained from young men. However, the concentration of alpha 2-adrenergic receptor agonist to trigger the secondary aggregation response did not vary with age. There was no difference in the responsiveness of platelets from young and elderly women for either the primary or secondary aggregation response. We conclude that platelet alpha 2-adrenergic receptor responsiveness is increased with age rather than decreased, as predicted from some studies of the density of platelet alpha 2-adrenergic receptors and their coupling to adenylyl cyclase. Furthermore, the increase in alpha 2-adrenergic receptor responsiveness is gender specific.