The trajectories of sympathetic nerves projecting to orbital targets were determined in adult rats with intact innervation and following acute sympathetic denervation, neonatal unilateral superior cervical ganglionectomy, or unilateral ganglionectomy on postnatal day 30. Sympathetic nerves were identified by using immunofluorescence for the noradrenergic transmitter enzyme dopamine beta-hydroxylase and by using catecholamine histofluorescence. In rats with intact innervation, sympathetic fibers travel to the orbit in association with the abducens, trochlear, and Vidian nerves. Within the retroorbital and retroocular connective tissue, the fibers redistribute to become associated with sensory-nerve branches of the trigeminal nerve, the orbital vasculature, and the periorbital sheath. Fibers reach their targets by traversing variable amounts of connective tissue of the periorbitum, the orbital septa, and the striated muscle epimysia. Following neonatal ganglionectomy, intracranial fibers of contralateral origin enter the orbit by traveling through connective tissue of the optic nerve meninges and lining the anterior lacerated foramen. These fibers travel independent of the trochlear, abducens, and Vidian nerves, but, otherwise, they use the same orbital pathways as those employed in the intact animal. In animals ganglionectomized on postnatal day 30, fibers enter the posterior portion of the orbit primarily via the optic foramen; they travel only short distances and end blindly in the periorbital sheath. These findings indicate that fascial structures are a major component of the pathways that guide sympathetic fibers to their appropriate targets both in normal development and during reinnervation following neonatal ganglionectomy. Because orbital connective tissues are termination sites of abortive fiber sprouting in older rats, developmental changes in the properties of these tissues may contribute to the absence of pathway formation in the mature animal.