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5-Fluorouridine (5-FUR), a ribonucleotide metabolite of 5-Fluorouracil (5-FU), is a more potent inhibitor of cellular proliferation and cell-mediated contraction in vitro than 5-FU. We compared the efficacy of these two drugs in a cell injection model of proliferative vitreoretinopathy using New Zealand albino rabbits. Forty-five eyes were divided into three groups and injected intravitreally with homologous fibroblasts. Eyes were examined at the time of injection and 7, 14, 21 and 28 days thereafter. By day 28, 70.5% (12 of 17) of 5-FUR treated eyes demonstrated no appreciable proliferative or tractional activity compared with 41.7% (5 of 12) of 5-FU treated eyes and 10% (1 of 10) of control eyes (p < 0.006). Medullary ray puckers developed in 29.4% (5 of 17) and 25% (3 of 12) of 5-FUR and 5-FU treated eyes respectively. No 5-FUR treated eye developed extensive tractional or combined tractional and rhegmatogenous retinal detachment compared with 33.3% (4 of 12) of 5-FU treated eyes and 80% (8 of 10) of control eyes (p < 0.001). These results suggest that 5-Fluorouridine may be more effective than 5-FU for the treatment of vitreoretinal scarring.