In a previous study (2), we showed that subclinical hypothyroidism is not rare among patients with episodes of major depression (5.3%) and that serum concentrations of thyrotropin, or thyroid-stimulating hormone (TSH), at or above the upper 25th percentile of the normal reference range may be associated with characteristics of severe major depression. Consequently, we systematically measured TSH, thyroxine (T4), and T3 serum levels in 101 consecutive patients hospitalized for episodes of major depression. The Hamilton Depression Rating Scale was administered at entry and after 28 days of antidepressant therapy. All patients gave written informed consent. The observer assessing scores on the Hamilton depression scale was unaware of serum thyroid hormone test results. Nine patients (9%) had serum TSH concentrations at or above the upper 25th percentile of the normal reference range (group A); only three (3%) had serum TSH concentrations higher than the upper limit of the normal reference range. All nine of these patients were women, and this sex distribution was significantly different from that for patients with serum TSH concentrations below the upper 25th percentile of the normal reference range (group B) (χ2=5.47, df=1, p<0.02). Group A had a higher serum TSH concentration than did Group B (mean=4.31 μIU/liter, SD=3.27; mean=1.13 μIU/liter, SD=0.55, respectively) (Mann-Whitney z=4.93, p<0.001) and a higher T3 concentration (mean=3.44 ng/ml, SD=7.10; mean=0.85 ng/ml, SD=0.22) (Mann-Whitney z=1.65, p<0.10) but not a higher serum T4 concentration (mean=10.14 ng/ml, SD=1.02; mean=10.71 ng/ml, SD=2.20).