Using semi-quantitative in situ hybridization, corticotropin-releasing factor (CRF) and CRF receptor 1 (CRF-R1) mRNA levels were determined in the rat hypothalamus and amygdala after short-term (10 days) and chronic (4 weeks) treatment with the antidepressant amitriptyline. We found that chronic treatment with amitriptyline produced a significant decrease in CRF mRNA (to 33% of control) in the hypothalamic paraventricular nucleus (PVN). Short-term or chronic amitriptyline treatment had no effect on CRF-R1 mRNA levels in the PVN. However, after chronic treatment, there was a significant decrease of CRF-R1 mRNA levels in the lateral + basolateral (to 60% of control), and in the medial (to 70% of control) amygdala nuclei. These results suggest that the tricyclic antidepressant amitriptyline may exert part of its effects through modulation of hypothalamic CRF and of CRF-R1 gene expression in the amygdala.