Orexin-A and orexin-B (also known as hypocretin-1 and hypocretin-2) are hypothalamic peptides that regulate feeding behavior, energy metabolism, and sleep-wake cycle. We determined the distribution of orexin-A and -B in the rat spinal cord, using sensitive radioimmunoassays and an immunohistochemical technique with three antisera specific for these orexins. Orexins were distributed throughout the spinal cord, and their contents were highest in the cervical region. Orexin fibers were concentrated in lamina I of the dorsal horn and area X surrounding the central canal of the spinal cord. Abundant orexin fibers also were present in the preganglionic sympathetic and parasympathetic cell columns. These findings suggest that orexins in the spinal cord may be involved in the modulation of sensory informations and the autonomic system as neurotransmitters or neuromodulators, both.