Platelet 3H-imipramine binding and monoamine oxidase (MAO) activity were investigated in elderly outpatients with primary major depression, and in a group with depression secondary to medical illness (organic mood disorder, depressed by DSM-III-R criteria) in a multidisciplinary geriatric clinic. The density of the binding of 3H-imipramine (Bmax) was decreased significantly in subjects with major depression compared to subjects with secondary depression, and to controls. There was no difference in Bmax values between subjects with secondary depression and controls. MAO activity was increased in the group with secondary depression, but not in the group with primary major depression. These results provide preliminary evidence for the relative specificity of platelet 3H-imipramine binding as a marker for primary major depressive disorder compared to secondary depression in medically ill elderly people, supports the concept of biological heterogeneity in secondary depression, and extends the findings of decreased Bmax values in two previous studies in non-medically ill depressed elderly patients.