The effects of endothelin-1 (ET-1) on intraocular pressure (IOP) and aqueous humor dynamics were studied in the rabbit eye. The intravitreal injection of 10(-5) M ET-1 (20 microliters) produced a biphasic IOP response consisting of an initial rise of 1 to 2 hours in duration, and a subsequent prolonged reduction lasting for more than 96 hours. Aqueous humor dynamics were determined 24 hours after the 10(-5) M ET-1 injection. Aqueous humor formation, measured fluorophotometrically, was decreased by 58%. Total outflow facility increased by 94%, according to measurement by two-level constant pressure perfusion. The change of uveoscleral outflow determined by fluorescein-dextran perfusion was not significant. The decrease in aqueous flow and the increase in total facility accounted for most of the IOP reduction after the ET-1 injection. Endothelin, which is endogenously present in the eye, may play a role in the regulation of intraocular pressure.