The function of the alpha-2-receptor and intracellular effector systems was examined in 39 panic disorder patients and 30 healthy subjects using the platelet as a model system. Alpha-2-receptor density, as reflected by 3H-yohimbine binding, was not different between the two groups. Platelet alpha-2-receptor affinity was decreased (higher Kd) in the panic disorder patients. Other significant abnormalities in the patients included a decreased basal adenylate cyclase activity, reduced EC50 for the epinephrine inhibition of adenylate cyclase activity, and decreased stimulation of adenylate cyclase activity by prostaglandin E1 and sodium fluoride. These results are consistent with a dysfunction in some panic disorder patients at the level of the stimulatory GTP binding regulatory protein, Gs, or the adenylate cyclase catalytic unit. The relationship of these findings to previous studies of noradrenergic function in panic disorder patients is discussed.