OBJECTIVE: Greater activity of the hypothalamic-pituitary-adrenal (HPA) axis is associated with specific neurological and psychiatric disorders, including Alzheimer's disease and depression. Hyperactivation of paraventricular corticotropin-releasing hormone (CRH) neurons may form the basis of this increased activity of the HPA axis. METHOD: Activation of the CRH neurons was determined through measurement of the amount of CRH-mRNA in the paraventricular nucleus by using quantitative, in situ hybridization histochemistry with systematically sampled frontal sections through the hypothalamus of routinely formalin-fixed and paraffin-embedded autopsy brain material of 10 comparison subjects, 10 patients with Alzheimer's disease, and seven depressed patients. RESULTS: CRH-mRNA levels in the paraventricular nucleus of Alzheimer's patients were markedly higher than those of comparison subjects, whereas CRH-mRNA levels in the paraventricular nucleus of depressed patients were even higher than the levels of Alzheimer's patients. CONCLUSIONS: Paraventricular CRH neurons in Alzheimer's disease and depression are hyperactivated, and this hyperactivation may contribute to the etiology of these disorders.