3-Methoxy-4-hydroxyphenylglycol (MHPG), the urinary metabolite thought best to reflect brain norepinephrine metabolism, was studied in a large group of hospitalized depressed patients with primary affective disorder and in normal controls, as part of an ongoing effort to evaluate the role of central amine dysfunction in affective illness. Overall there was no difference in MHPG between the depressed patients and controls. Hosever, within the depressed population the bipolar patients excreted significantly less MHPG than the unipolars and, as a group, the male bipolar patients had significantly lower MHPG than male controls. MHPG correlated positively with age, age of onset, rating of anxiety and psychosis and, most importantly, with systolic blood pressure. These data support the concept of biological heterogeneity among individuals with major depressive disorders. However, the relationship between MHPG excretion and various psychological and physiological parameters is both intriguing and complex and warrants careful interpretation.