In cynomolgus monkeys, PGF2 alpha when topically applied in the isopropylester form in doses sufficient to reduce IOP, has much less effect on the ciliary epithelium than PGs have previously been reported to cause in rabbits. We observed no accumulation of wandering cells (leukocytes and histiocytes), which are one of the typical signs of inflammation. The changes noted in the ciliary epithelium itself were mild, which may either be a sign of mild inflammation or might be caused by the greatly reduced IOP and consequent alteration in internal pressure relationship. The functionally important morphological effect of PGF2 alpha seems to be a widening of the uveoscleral pathways within the ciliary muscle, which seems primarily to be a result of relaxation of the muscle fibers and secondary to loss or modification of extracellular material. Preliminary studies indicate that both of these morphological alterations are at least partly reversed within 12 hours after the last PG treatment. This is consistent with the concept that the observed morphological changes in the ciliary muscle are associated with the ocular hypotensive effects of PGF2 alpha since such hypotensive effects are usually maintained for less than 12 hours after the topical application of this drug. Our findings suggest that PGF2 alpha-IE and possible other PGs, may provide a useful new tool to reduce IOP and to explore the physiological and pharmacological mechanisms that are involved in the control of uveoscleral outflow.