Endothelin-1 (ET-1) is a potent vasoconstrictive peptide produced in part by vascular endothelial cells. In order to investigate its effects on the episcleral vascular system and intraocular pressure (IOP), we injected ET-1 (3, 10, 30, 100, 300, 1,000 pmol) into the subconjunctival space of rabbits and measured IOP with a manometer. Injection of a dose higher than 10 pmol caused a transient increase of IOP. Mean maximum elevation rate of IOP for each dose of ET-1 was 14.9 +/- 0.9%, (mean +/- standard error) 43.5% +/- 9.5%, 40.8 +/- 7.5%, 46.9 +/- 9.8%, and 84.1 +/- 22.6. Next, we injected 1,000 pmol into the subconjunctival space, and continuously measured IOP and ocular pulse pressure with a manometer. IOP increased rapidly after ET-1 injection. Maximal increase of IOP was observed at 22.7 +/- 9.2 min after ET-1 injection, and IOP decreased after the peak. The ocular pulse pressure increased with IOP elevation and decreased with the IOP reduction. We speculated that the transient elevation of IOP was caused by increase of aqueous outflow resistance, and the decrease of IOP was caused by decrease of aqueous outflow resistance and decrease of blood flow in the ciliary body and the choroid. This strongly suggests that subconjunctival injection of ET-1 could have a large effect on the episcleral vascular system, aqueous outflow, and blood flow in the ciliary body and the choroid.