The hippocampus/subiculum has been hypothesized to restrain hypothalamically mediated neuroendocrine responses to psychological stressors. While psychological stress has been observed to restrict plasma vasopressin (AVP) secretion, the role of these brain structures has not been examined. We subjected rats with bilateral aspiration of the hippocampus and controls with bilateral aspiration of the overlying neocortex to a 45 s swim stress. Plasma AVP and relevant AVP stimuli were measured at 30 min intervals for 90 min following the stressor. Immediately following the stressor, AVP levels were similar in the two groups, and then rose in hippocampal-lesioned animals to a greater extent than in the controls. None of the measured AVP stimuli could account for this difference. We conclude that rats with hippocampal lesions demonstrate increases in plasma AVP following psychological stress.