The purpose of this study was to examine the integrity of the blood-spinal cord barrier after intrathecal administration of endothelin-1 (ET-1) in the rat spinal cord. A laser Doppler probe was positioned in the exposed subarachnoid space at the T8 vertebral level. In the first experiment, horseradish peroxidase (HRP), a marker of barrier integrity, was given intravenously prior to the intrathecal application of ET-1. Blood flow was then recorded for 3 h, after which the anesthetized animals were euthanized. In the second experiment, animals exposed to endothelin were recovered after confirming a 50% reduction in blood flow. HRP was given 10 min prior to euthanasia at 24 h post infusion. The intensity of staining for HRP was quantified by optical density in fixed sections of spinal cord. There was a significant sustained reduction in spinal cord blood flow and significant barrier breakdown to HRP at both 3 and 24 h after administration of the peptide. Based upon these results we conclude that intrathecal infusion of ET-1 reduces spinal cord blood flow and results in prolonged breakdown of the blood-spinal cord barrier.