These studies sought to determine whether the cell bodies of rat superior cervical ganglion neurons projecting to three very different target organs differ in terms of their size, number, location within the ganglion and/or neuropeptide content, and whether these features are altered in response to neonatal deafferentiation of the ganglion. A series of retrograde tracer, immunocytochemical, and double-labeling studies revealed differences in the size, number, location and neuropeptide content of superior cervical ganglion neurons that project to the submandibular salivary glands, eyes, or pineal gland. The mean areas of the cell bodies of neurons projecting to the submandibular gland are largest, those projecting to the eye are smallest, and those projecting to the pineal are intermediate in size. Submandibular gland projecting neurons are found throughout the ganglion, while the eye and pineal projecting populations are localized to the rostral quadrants. The different subpopulations of target organ specific superior cervical ganglion neurons are heterogeneous in their content of vasoactive intestinal peptide-, neuropeptide Y- and somatostatin-like immunoreactivity. A greater percentage of submandibular gland than of pineal projecting neurons display vasocative intestinal peptide-like immunoreactivity, but there are no differences in the percentage of neurons displaying neuropeptide Y- or somatostatin-like immunoreactivity between the target organ specific groups. Neonatal deafferentiation does not result in changes in the size, number or distribution of target organ specific neurons, or in the percentage of immunoreactive neurons in these populations. In conclusion, these studies provide evidence that the size and distribution of neurons and percentage of peptide-containing neurons in the superior cervical ganglion is related to the target organ innervated, but provides no evidence of exclusive target organ-peptide relationships.