This was a double-masked, randomized, paired comparison with vehicle trial of a topically administered prostaglandin (PG)E2 in healthy human volunteers. A statistically significant decrease of the intraocular pressure in these non-glaucomatous volunteers occurred at six hours following one drop of 0.02% solution that persisted to the last measurement of IOP at the 24 hour examination. Significant elevation in the intraocular pressure was present at one and two hours following the eye drop instillation. All volunteers reported transient ocular side effects related to drug administration, including mild eye ache and intermittent photophobia for a duration of 2 to 4 hours. These symptoms were associated with a transient conjunctival vasodilation, but with no evidence of anterior chamber cells and flare or ciliary flush as determined by slit lamp examination. The results of this study suggest that PGE2, or a derivative, may offer a new class of topically effective ocular hypotensive agents useful in lowering the intraocular pressure of glaucoma patients.