The studies presented demonstrate changes in hypothalamo-pituitary-adrenocortical secretion, and in electrical activity and synaptic responses of neurons in the bed nucleus of the stria terminalis, preoptic area, and hypothalamic paraventricular nucleus of rats exposed to early, long-term social isolation. Rats isolated from all social contact from an early preweaning time showed reduced basal plasma corticosterone concentrations, compared with littermate controls raised under social conditions. Isolated animals also exhibited a selective decrease in the spontaneous electrical activity of neurons within the hypothalamic paraventricular nucleus and lateral preoptic area, but not in adjacent structures. Moreover, isolation also altered the response of neurons in certain nuclei to electrical stimulation of the medial amygdala. Thus, a reduction in excitatory responses, and an increase in inhibition and nonresponsiveness, of preoptic area and paraventricular nucleus neurons was recorded, compared with control rats. Neurons in the bed nucleus of the stria terminalis were less affected, but showed an increase in the duration of excitatory responses following medial amygdala stimulation. These results, obtained from urethane-anesthetized rats, together with the reduced basal plasma corticosterone concentrations, suggest a reduction in limbic-hypothalamo-pituitary-adrenocortical (LHPA) activity following maternal deprivation and prolonged social isolation. This may result from altered limbic activity, specifically in the amygdala and its pathways to the paraventricular nucleus (PVN). Such alterations may include the stria terminalis, in so much as increased efficacy of inhibitory components and reduced efficacy of excitatory components was observed. The neural mechanisms underlying these alterations could involve an altered synaptology of the regions examined and/or a disruption of glucocorticoid feedback events.