Endothelin-1 (ET-1) reduced intraocular pressure (IOP) in animals when administered topically. The time-course of IOP changes induced by ET-1, however, has not been fully documented. We studied the IOP response to different doses of intravitreally injected ET-1 ranging from 10(-7) to 10(-4) M in rabbits. In each animal one eye received 20 muL of ET-1 solution and the contralateral eye received the same amount of vehicle in a randomized, masked fashion. IOP was measured by a pneumatonometer prior to and periodically for at least 72 hours after the intravitreal injection. ET-1 in 10(-4) and 10(-5) M concentration elicited an IOP response consisting of an initial rise of 1- to 2-hour duration, and a subsequent prolonged reduction lasting for more than 72 hours. The use of 3 x 10(-6) and 10(-6) M solutions resulted in a prolonged IOP reduction without an early IOP rise. No significant IOP change was induced by 10(-7) M solution or the vehicle. No change was observed in pupillary diameters after injection of ET-1 in any dose. The aqueous prostaglandin E2 concentration was significantly increased at both 1 and 24 hours after 10(-5) M ET-1 injection.