SUMMARY The effects of ether stress and of photic and acoustic stimulation on adrenocortical responses were studied in normal rats and in rats with bilateral lesions in the medial forebrain bundle (MFB). While the response to ether stress was slightly reduced, the neurogenic stimuli produced much lower plasma corticosterone levels in the lesioned animals compared with intact rats. The neural pathways and the role of the MFB in mediating adrenocortical responses to neurogenic stimuli are discussed. The present results demonstrate that the MFB is the main final afferent pathway through which neural impulses to the hypothalamus are propagated, thus activating the secretion of adrenocorticotrophin.