High-affinity 3H-imipramine binding to platelets was determined in 15 drug-free unipolar depressed women and 15 normal controls. The maximum number of binding sites (Bmax) was lower in the depressed population, but the difference fell short of statistical significance (p = 0.07). The dissociation constant for imipramine binding (Kd) was found to be significantly lower among patients than in controls (p = 0.02). The various factors that can affect the in vitro platelet assay, and the implications for affective disorder research, were discussed.