Topically applied prostaglandin F2 alpha (PGF2 alpha) has been shown to lower intraocular pressure in cynomolgus monkeys. In this study the morphological changes following topical treatment of seven cynomolgus monkeys with 4 micrograms PGF2 alpha isopropylester for 5-8 days were investigated and compared with the eyes of five normal animals. Quantitative light microscopical, ultrastructural and immunhistochemical methods were used. No cellular signs of inflammation were seen in any of the eyes. Slight edema in the most anterior part of the ciliary processes occurred in most eyes, but only in parts of the circumference. The most pronounced change was dilation of the intramuscular spaces within the ciliary muscle. No changes were observed in the extracellular matrix within the muscle bundles, which consist partly of type IV and VI collagen, laminin and fibronectin. In the connective tissue between the muscle bundles, loss of collagen type I and III fibrils was observed. Additionally, macrophages were found with phagolysosomes containing phagocytized collagen fibrils. We suggest that loss of extracellular material leads to a widening of the uveoscleral outflow pathways of ciliary muscle and thereby to a reduction in intraocular pressure.