The role of the amygdaloid complexes in the compensatory hypersecretion of ACTH following adrenalectomy was studied in the adult male rat. Unilateral or bilateral radiofrequency or knife-cut lesions were placed in the amygdalae, their efferent pathways or the septal region. Three weeks following adrenalectomy resting plasma ACTH concentrations were measured by radioimmunoassay. Bilateral lesions of a direct medial-projecting portion of the ventral amygdalo-hypothalamic pathway blocked the compensatory hypersecretion of ACTH following adrenalectomy. A unilateral complete amygdalar lesion coupled with destruction of the same direct amygdalo-hypothalamic pathway on the opposite side had the same positive effect. In contrast, unilateral destruction of the direct amygdalo-hypothalamic projections, ablation of the septum, or bilateral destruction of the stria terminalis did not block hypersecretion of ACTH following adrenalectomy. These data suggest that the amygdalae and their direct hypothalamic projections, but not the stria terminalis or septum, are essential for the hypersecretion of ACTH following adrenalectomy. Furthermore, one amygdaloid complex appears sufficient for this effect. It is possible that the amygdalae act as a central nervous system ‘glucocorticoid-sensor’ in the modulation of ACTH secretion in the