The serum levels of thyroxine and triiodothyronine (T4 and T3) were investigated at 10 different time points during a 24 h period in 31 inpatients meeting the RDC criteria for acute major depressive disorder. Twenty-three of these patients were also reinvestigated in a state of partial or complete remission. The results show that there was no significant difference in T4 or T3 levels during the 24 h period between depressed patients and 32 healthy controls despite significantly decreased TSH levels and TSH response to TRH administration (delta TSH) in the patient group. No indications were obtained that the patients' clinical presentation or depressive symptomatology as revealed by their CPRS scores, psychotropic medication, melatonin levels, or the outcome of the dexamethasone test, significantly influenced the T4 or T3 levels. The depressed patients who were studied longitudinally showed increased T4 levels in the acute phase compared to remission, whereas the T3 levels did not change. However, the levels of thyroid hormones were within the normal range in the acute phase as well as in remission. Furthermore, the changes in thyroid hormones between the state of relapse and remission were not significantly correlated to the corresponding increase in TSH levels and delta TSH between the two assessments. The present results are consistent with the hypothesis that the mechanism behind the impaired TSH response to TRH in acute major depressive disorder is a downregulation of the pituitary TRH receptors.