Using immunohistochemical methods, substance P is localized to nerves of the human eye. Immunoreactive nerve fibers occur in the cornea, about limbal blood vessels, and within the trabecular meshwork. Substance P-like immunoreactive nerve fibers surround uveal blood vessels, especially in the choroid and ciliary body. Immunoreactive nerves are seen in ciliary processes. The ciliary muscle is innervated, as are the iris dilator and sphincter muscles. Apposition of immunoreactive nerves to uveal melanocytes is apparent. The distribution of substance P-like immunoreactive nerves in the human eye parallels that found in other mammals. While substance P probably has important neurotransmitter or neuromodulator roles in the eye, further physiologic studies are required to define its ocular function.