• Vasoactive intestinal polypeptide (VIP) is a biologically active neuropeptide found in both the peripheral and the central nervous systems. Previous studies have shown that VIP-like immunoreactive nerves are present in the uveal tissues of the human eye. The distribution of VIP-like immunoreactivity of the human lacrimal gland and sphenopalatine ganglion was studied. A lacy network of VIP-like immunoreactive nerve fibers was found in the lacrimal gland and was predominantly located along the basilar surface of the acinar epithelium and in the interstitial connective tissue of the gland. This pattern of innervation was nearly identical to the distribution of cholinesterase-positive fibers in human lacrimal glands. The VIP-like immunoreactive cell bodies were found throughout the sphenopalatine ganglion obtained at autopsy. The distribution of VIP-like immunoreactive nerves in the human lacrimal gland and sphenopalatine ganglion was generally similar to that described in mammalian and avian systems, although some differences were noted. Vasoactive intestinal polypeptide may represent an important cotransmitter or neuromodulator for the facial parasympathetic nerves that supply the eye and the lacrimal gland.