The affinity (1/Kd) and density (Bmax) of α2-adrenoreceptors in platelet membranes were studied in patients with major depressed illness (n = 10), affected first-degree relatives (n = 17), nonaffected first-degree relatives (n = 44) and controls (n = 31). The α2 selective antagonist 3H-yohimbine was used as the radioligand. The mean Bmax values of affected subjects (probands and relatives) were significantly lower than those of controls. There was no difference in Kd values between the controls and affected subjects. There was a positive gradient of the mean Bmax values from the groups of probands to affected relatives, unaffected relatives and control subjects. A familial effect of Bmax values between members of the same families confirms a genetic control of α-receeptor affinity. These results support the hypothesis that the density of α2-adrenoreceptors, evaluated by 3H-yohimbine binding on human platelets, could be a potential vulnerability marker for affective disorder.