Prostaglandins (PGs), or their derivatives, are potent ocular hypotensive agents which may prove useful in glaucoma therapy. PGF2 alpha (250 micrograms in 50 microliter saline) or epinephrine 2% solution (50 microliter) was topically applied twice daily for 2 weeks to one eye of six cynomolgus monkeys for each agent. Contralateral control eyes received their respective vehicles. By light microscopy, there was no evidence of inflammation, corneal changes, retinal pathology (including cystoid macular edema), or other adverse effects. Likewise, by electron microscopy of the peripheral cornea, anterior chamber angle, iris base and ciliary body, no differences were noted between treated and control eyes. Therefore, multiple dosing with PGF2 alpha in subhuman primate eyes did not result in notable histopathological changes that would contraindicate a clinical trial in glaucoma patients.