Endothelin-1 (ET-1) reduces intraocular pressure (IOP) in animals when administered topically. The time course of IOP induced by ET-1, however, has not been fully elucidated. We studied the IOP response to different doses of ET-1 ranging from 10(-7) to 10(-4)M (5 micrograms to 5 ng) intravitreally injected in rabbits. In each animal one eyes received 20 microliters of ET-1 solution and the contralateral eye received same amount of vehicle in a randomized, masked fashion. IOP was measured by a pneumotonometer prior to and periodically for at least 72 hours after the intravitreal injection. ET-1 in 10(-4) and 10(-5) molar concentration elicited a biphasic IOP response consisting of an initial rise of 1 to 2 hours duration, and a subsequent prolonged reduction lasting for more than 72 hours. 3 x 10(-6) and 10(-6) M solution resulted in a prolonged IOP reduction without an early IOP rise. No significant IOP change was induced by 10(-7) M solution or vehicle. Both IOP rise and reduction were significantly related to the dose of ET-1.