Platelets from two patients with essential thrombocythemia failed to aggregate or release serotonin in response to concentrations of epinephrine that aggregated platelets from normal controls. Therefore, we studied their alpha-adrenergic receptors, using 3H-dihydroergocryptine (3H-DHE), an alpha-adrenergic antagonist. These platelets contained an average (mean +/- S.E.) of 210 +/- 18 and 227 +/- 27 3H-DHE binding sites per platelet--less than half that found on control platelets, 464 +/- 37 (P less than 0.01). In contrast, platelets from two other patients with essential thrombocythemia responded to epinephrine and contained a normal number of 3H-DHE sites. Platelets in essential thrombocythemia demonstrated normal kinetics of 3H-DHE binding and normal affinities for 3H-DHE and for epinephrine. When control platelets were preincubated with a half-saturating concentration of 3H-DHE, there was a diminution of epinephrine-induced platelet function comparable to that seen in essential thrombocythemia. Thus, a deficiency of alpha-adrenergic receptors may account for diminished functional responsiveness of platelets to epinephrine in some patients with essential thrombocythemia.