The serum levels of thyroid hormones and thyrotropin (TSH) were evaluated before and after 8 PM and 11 PM thyrotropin-releasing hormone (TRH) challenges, on the same day, in 41 drug-free DSM-III-R euthyroid major depressed inpatients and 16 hospitalized controls. Depressed patients exhibited elevated circulating concentrations of thyroid hormones, which were associated with and may have contributed to the blunted TSH response to TRH. This was confirmed by: (a) higher basal levels (albeit not always statistically significant) of free triiodothyronine (FT3B) and free thyroxine (FT4B) at 8 AM and 11 PM in the depressed patient population compared with the controls; (b) lower basal levels of TSH in the depressed subjects (even though this was only statistically significant at the 11 PM sampling) compared with the controls; (c) blunted TSH response to TRH (delta TSH) in the depressed group (although this was only statistically significant at 11 PM) and blunted delta delta TSH values (differences between 11 PM-delta TSH and 8 AM-delta TSH).