Thyrotropin-releasing hormone (TRH) is a tripeptide and acts as a stimulator of the pituitary-thyroid axis as well as having a great number of well defined extrathyroidal functions. Studies in experimental animals have shown, that TRH also has a role as a neuromodulator within the autonomous nervous system. In this study we analyzed the effects following peripheral administration of TRH (200 micrograms, 400 micrograms) in patients with endocrinological disorders and in healthy females and males. By means of a questionnaire, patients were asked about possible (side-) effects; ventilatory and cardiovascular monitoring was performed during steady state. The pulsatile TSH-secretion pattern was analyzed and thyroid and stress hormones were measured in the blood prior to and following TRH i.v. Frequent symptoms afer TRH were feeling of heat (58%), stimulation of respiration (61%), palpitations (39%), micturition urge (52%) and restlessness (32%). Apparative monitoring demonstrated a short stimulation of respiration and an increase of heart rate. After 400 micrograms TRH i.v., blood levels of ACTH decreased slightly (p less than 0.01) but levels of T3, T4, epinephrine, norepinephrine and cortisol remained unchanged (p greater than 0.05). TSH-levels were low during daytime and showed a surge at night.