Inthese three experiments, we investigated the effect of adrenalectomy and adrenal demedullation on the stress-induced impairment of long-term potentiation (LTP) in the rat hippocampal slice. In the first, adrenalectomy alone resulted in a significant reduction in LTP, while exposure to stress resulted in a further reduction. In the second, replacing corticosterone in adrenalectomized rats did not restore LTP. In the last experiment, demedullation resulted in a reduction in LTP similar to that induced by adrenalectomy, while exposure to stress did not result in a further reduction. In combination, these studies provide evidence that the adrenal medullary system modulates hippocampal plasticity and the stress-induced impairment of LTP.