Marked vasodilation followed by a rupture of the blood aqueous barrier is the best-documented hypothesis to explain the rise of intraocular pressure (IOP) induced by prostaglandins (PGs) or their precursors. However, a direct action on secretory mechanisms in the ciliary processes may not be excluded. To explore the latter possibility, compounds capable of decreasing IOP by different mechanisms have been tested in rabbits for their effects on experimentally elevated IOP induced by arachidonic acid (AA) and PGE<sub>2</sub>. Topical administration of 50 μ1of 0.5% AA or 0.01% PGE<sub>2</sub> solutions was utilized as standard ocular hypertensive doses. Epinephrine, norepinephrine, phenylephrine and isoproterenol administered topically and acetazolamide administered orally were tested for their effects on the IOP response to AA and PGE<sub>2</sub>. The IOP elevation due to AA instillation was studied at 30 min and 4 h after administration of the test agents. Only one experimental time (30 min) was used for PGE<sub>2</sub> to confirm the data obtained with AA. At 30 min, α- and mixed αβ-adrenerig agonists inhibited in a dose-related manner the PG-mediated elevation of IOP. In contrast, they did not affect these reactions at 4 h when their ocular hypotensive effect was maximal. The β-adrenergic agonist and acetazolamide did not influence AA or PG responses at either experimental time. The inhibition observed with epinephrine, norepinephrine and phenylephrine was attributed to their vasoconstrictive properties rather than to an effect on aqueous humor secretory mechanisms. These results argue against the formulated hypothesis that PGs elevate IOP by a direct action on secretory mechanism and give additional evidence for a vascular effect of PGs on the eye.