Prostaglandin F2 alpha(PGF2 alpha) as its tromethamine salt was topically applied, and hypotensive and other ocular effects were studied, in glaucomatous human eyes. After baseline intraocular pressure (IOP) measurements, 100 mu g PGF2 alpha tromethamine salt dissolved in 50 mu l saline was applied to 23 glaucomatous eyes of 20 patients. The pretreatment diurnal IOP values of the same eye served as control group. It was found that in comparison with baseline values, PGF2 alpha caused significant but transient elevation in IOP in the first half-hour (mean 1.95 mm Hg, p < 0.01), but it decreased below baseline values at the first hour. A significant decrease in IOP from baseline was observed at the 2nd hour (p < 0.05), which became more prominent between the 4th and 24th hours (p < 0.001). PGF2 alpha produced a maximal IOP reduction of 10.21 mm Hg at the 12th hour (p < 0.001). The IOP differences between PGF2 alpha-treated and control groups were significant between the 4th and 24th hours (p < 0.001), with the maximal IOP difference of 9.21 mm Hg at the 12th hour (p < 0.001). PGF2 alpha caused marked conjunctival hyperaemia in all eyes. Aqueous flare and cellular response were not seen in any of the eyes. Half of the patients experienced ocular smarting or a foreign-body sensation, periocular pain and headache. PGF2 alpha reduced IOP effectively in glaucomatous human eyes.