Human CRH (hCRH), which acts as a major neuroregulator within the hypothalamic-pituitary-adrenal axis, is also a respiratory stimulant. The broad distribution of CRH receptors in brain areas involved in respiratory regulation is consistent with this finding. This study was designed to investigate whether ACTH or cortisol mediates the respiratory stimulation effect of CRH. Bolus injection of 100 micrograms hCRH induced significant respiratory stimulation in all 10 normal subjects studied. hCRH given after the administration of 2 mg dexamethasone, which greatly reduced plasma cortisol levels, had the same respiratory effect on respiration. Thus, increase in plasma ACTH and cortisol concentrations are probably not involved in the respiratory analeptic effect of CRH.