The effects of intracameral injection of three endothelin isopeptides (ET-1, ET-2 and ET-3) were studied in the rabbit eye. All three peptides at pmol doses caused a dose-dependent rise in intraocular pressure (IOP) and an increase in protein concentration in the aqueous humor, indicating breakdown of the blood-aqueous barrier. Mean arterial blood pressure was not affected. ET-1 was more effective to increase IOP than were ET-2 and ET-3 whose effects seemed to be equal. ET-1 also caused vasodilation in the anterior uvea. The effects of ET-1, ET-2 and ET-3 on the IOP and blood-aqueous barrier, as well as the effects of ET-1 on regional blood flow in the eye, were abolished by pretreatment with indomethacin. Injection of 4 pmol ET-1 into the anterior chamber caused an increase in the concentration of prostaglandin E2 (PGE2) in the aqueous humor, most probably as a result of increased production of PGE2 in the anterior uvea. The results indicate that the effects of ET-1, ET-2 and ET-3 in the rabbit eye are to a large extent mediated by arachidonic acid metabolites.