This study describes the effect of the adrenocortical inhibitor (metyrapone) on the activity of the brain-hypophyseal-interrenal system of Liza ramada mature females after handling and confinement stress. Adrenocorticotropin hormone (ACTH) and corticotrophin-releasing factor (CRF) are immunocytochemically localized in the pituitary and brain, respectively, and this suggests that CRF may mediate the ACTH release. During metyrapone administration, the brain's CRF-immunoreactive cells displayed an increase in their secretory and synthetic activity. During metyrapone administration to L. ramada mature females, the secretory activities of CRF-immunoreactive cells showed an increase after the first and second injections as reflected by degranulation and vacuolization. The secretory activity of injected females with 100 mg/ kg metyrapone was higher than that observed for the dose of 20 mg/ kg metyrapone. Also, ACTH-immunoreactive cells showed an increase in secretory activity during the first two injections as indicated by weak immunoreactivity. After the third injection of metyrapone, the synthetic activity of both CRFand ACTH-immunoreactive cells was augmented as indicated by the increase in the immunoreactive staining intensity and granulation. Handling and confinement stress significantly increased the cortisol levels in both L. ramada control females and females injected with high doses of metyrapone, however low doses of metyrapone decreased cortisol levels. Therefore, when using the drug to examine the functional role of glucocorticoids, attention should be paid to these properties. It is concluded that metyrapone is suitable for stress control during the handling and confinement of L. ramada prespawning female.