The effects of 14 successive daily subconjunctival 5-fluorouracil (5-FU) injections on corneal endothelial and ciliary epithelial cells were studied in pigmented rabbits. A total of 100 microliters 5% or 1.25% 5-FU was injected subconjunctivally in one eye and vehicle solution was injected in the other eye. At 12 h or 14 days after the 14th and last injection, both eyes were processed for observation with scanning or transmission electron microscopy. In other groups of rabbits injected with 5% 5-FU, effects on the corneal thickness, corneal endothelial permeability, blood-aqueous barrier permeability, intraocular pressure and aqueous flow rate were also studied. In the fellow eyes and treated eyes examined 14 days after the last injection, no significant morphological changes were seen. In eyes examined 12 h after the last injection, the following findings were obtained. The corneal endothelial cells showed moderate cytoplasmic swelling and mitochondrial swelling and vacuolation. The changes were dose-dependent and most marked in the area near the injection site, whereas they were minimal in the area apposing it. In the ciliary body adjacent to the injection site, disarrangement of the basal infoldings of non-pigmented epithelial cells was seen in eyes injected with 5% 5-FU, whereas no significant change was observed in those injected with 1.25% 5-FU. However, the physiological parameters examined remained unaltered.