Four clinical studies were performed in 54 healthy Japanese volunteers to assess the efficacy and the safety of two phenyl-substituted PGF2 alpha-isopropyl ester analogues, PhXA34 and PhXA41 after both single and repeated administrations. PhXA34 and PhXA41 reduced intraocular pressure (IOP) significantly in a dose-dependent way. The maximum IOP reductions were 14.5% to 17.5% with baseline adjustment at 10 to 12 hours after a single administration. No transient early elevation in IOP after treatment was observed. Based on the maximum IOP reducing effect of 1 microgram of PhXA34 and PhXA41, PhXA41 appeared to be at least 1.5 times more active than PhXA34. Tachyphylaxis of the ocular hypotensive effect did not develop during repeated administration for 5 days. A mild conjunctival hyperemia occurred in some subjects at high doses; it tended to diminish with time during the repeated administration of both drugs. Neither PhXA34 nor PhXA41 caused any change at any time in the aqueous flare intensity measured with a laser flare-cell meter. There were no changes in pupillary diameter after treatment. Each drug was well tolerated and caused no other ocular or systemic side effects.