The 24 h serum levels of prolactin (PRL) and thyrotropin (TSH) assessed at ten different time points and the PRL and TSH responses to TRH administration (delta PRL, delta TSH) were investigated in 26 inpatients meeting the RDC criteria for an acute major depressive disorder. Fourteen of these patients were reinvestigated in a state of partial or complete remission. Comparison between the patients during both relapse and remission and 23 healthy controls showed no differences in the paramenters reflecting the 24 h PRL levels or delta PRL. However, significantly lower 24 h TSH levels and delta TSH were found in the patient group in the acute phase. Antidepressant medication, sedatives or the outcome of the dexamethasone test did not significantly influence the PRL levels or delta PRL. Both the patient group and the controls revealed normal sleep associated PRL release indicating unaltered serotoninergic and/or dopaminergic neurotransmission regulating the PRL secretion. The present results indicate a selective disturbance affecting the pituitary TSH secretion, and are consistent with our hypothesis that the mechanism behind the decreased TSH levels and the impaired TSH response to TRH in acute major depressive disorder involves a down-regulation of the pituitary TRH receptors.