The high-affinity binding of triatiated imipramine to platelet membranes was compared in samples from 16 untreated depressed women and 21 age-matched controls of the same sex. The maximal binding in the depressed group was significantly lower than that of the controls, although the affinity constants were similar. These results suggest that binding of tritiated imipramine in human platelets may represent a biochemical index of depression, possibly reflecting similar changes in the brain.