The binding to human platelets of 3H-para-aminoclonidine (3H-PAC), an alpha2 adrenoceptor partial agonist, appears to be altered in depressed patients. We observed that the parameters of 3H-PAC binding to purified plasma membranes from platelets of normal Red Cross volunteers, compare favorably to those reported for binding to normal human autopsy prefrontal cortical lysates. However, only purified plasma membranes from platelets yielded a close comparison. 3H-PAC binding to intact platelets from healthy volunteers was less than 10% displaceable by an alpha2 adrenoceptor antagonist and was therefore unquantifiable. A low percent of specific binding (approx. 35%) was also observed in washed platelet lysates, and the binding was not of very high affinity (KD greater than 10 nM). In contrast, the binding of 3H-PAC to platelet purified plasma membranes from healthy subjects displayed two high affinity binding sites (KD1 = 10.6 pM and KD2 = 1.2 nM). These results are discussed in relation to our recent finding of elevated 3H-PAC binding to platelet purified plasma membranes from depressed patients as compared to healthy subjects.