Urinary 17-hydroxycorticosteroids (17-OHCS) were determined in 97 depressed patients previously classified as having unipolar or bipolar affective illness. Excretion of 17-OHCS was significantly lower in patients with a history of hospitalization for mania (bipolar) as compared to patients with no history of mania (unipolar), and to a smaller group with histories of recurrent depression interspersed with periods of increased activity or euphoria, but who never experienced clear-cut mania (unclassified). This finding was demonstrated in male and female patients. Severity of depression as measured by a global depression rating scale and subscales for anxiety and psychosis was not different for the various patient groups, although our clinical impression has been that depressed bipolar patients tend to be "retarded" whereas unipolar patients may be either "agitated" or "retarded." Data from this study suggest biological differences in patients classified according to a unipolar-bipolar format.