The paraventricular nucleus of the thalamus (PVT) is a midline thalamic nucleus with projections to limbic forebrain areas such as the nucleus accumbens and amygdala. The orexin (hypocretin) peptides are synthesized in hypothalamic neurons that project throughout the CNS. The present experiments were done to describe the extent of orexin fiber innervation of the PVT in comparison to other midline and intralaminar thalamic nuclei and to establish the location and proportion of orexin neurons innervating the PVT. All aspects of the anteroposterior PVT were found to be densely innervated by orexin fibers with numerous enlargements that also stained for synaptophysin, a marker for synaptic vesicle protein associated with pre-synaptic sites. Small discrete injections of cholera toxin B into the PVT of rats resulted in the retrograde labeling of a relatively small number of orexin neurons in the medial and lateral hypothalamus. The results also showed a lack of topographical organization among orexin neurons projecting to the PVT. Previous studies indicate that orexin neurons and neurons in the PVT appear to be most active during periods of arousal. Therefore, orexin neurons and their projections to the PVT may be part of a limbic forebrain arousal system.