Platelet alpha 2-adrenergic receptor binding sites were measured in a group of patients with major depressive disorder (MDD) (n = 23) and in normal controls (n = 25). When all depressed subjects were compared to controls, there were no differences in either Kd (affinity of the ligand) or total binding site (number/platelet), although a significant change in the ratio of high to low affinity states was observed in the depressed group. When the depressed patients were subdivided into those with and without a co-occurring borderline personality disorder (BPD), the BPD group had significantly fewer alpha 2 high affinity binding sites, while the group with depression alone had significantly more binding sites (both low and high affinity) than the control group. The results support the concept that assessment of comorbid diagnoses may be essential to biological studies of depression.