Substance P (SP)-containing nerve fibers are few in the rabbit cornea, which is richly supplied with acetylcholinesterase-positive nerve fibers, presumably sensory in nature. Treatment with capsaicin given by retrobulbar injection 48 h prior to sacrifice caused SP to disappear from the SP nerves in the cornea without affecting the acetylcholinesterase-positive nerve fibers. The corneal sensitivity to a tactile stimulus (wetted cotton swabs) and to a chemical stimulus (local application of capsaicin) and the disruption of the blood-aqueous barrier after local injury (infrared irradiation of the iris) were tested after pretreatment with capsaicin (retrobulbar injection) the SP antagonist [D-Pro2,D-Trp7,9]SP (single topical application or long-term application twice daily for 2 months), the local anaesthetic oxibuprocaine (topical application), or the neuronal blocker tetrodotoxin (intravitreal injection). All these treatments abolished or reduced the disruption of the blood-aqueous barrier after local injury but only oxibuprocaine and tetrodotoxin abolished the corneal sensitivity to tactile and chemical stimuli. It is suggested that SP nerve fibers constitute a minor proportion of the sensory nerve supply to the cornea, that the neurogenic mechanisms involved in the response to ocular injury differ from those involved in corneal nociception, and that uveal SP is involved in the response to ocular trauma and that corneal SP is probably not necessary for corneal nociception.