PURPOSE: To evaluate a new concept in pharmacological vitreolysis by studying the efficacy of intravitreal RGD peptide-assisted vitrectomy in facilitating the separation of the posterior cortical vitreous from the retinal surface in an animal model. METHODS: Eight rabbits (16 eyes) received an intravitreal injection of 1 or 5 mg of RGD peptide in one eye and either RGE peptide (inactive control) or phosphate buffered saline in the fellow eye. After 24 hours, a pars plana vitrectomy with low aspiration (< or =30 mmHg) was performed in an attempt to create a detachment of the posterior cortical vitreous. A masked observer performed pre- and postoperative indirect ophthalmoscopy and B-scan ultrasonography. Postoperative scanning electron microscopy evaluated the vitreoretinal surface in selected eyes. Two additional rabbits received intravitreal injections of RGD peptide in one eye (1 mg and 5 mg) and 1 mg of RGE peptide in the fellow eye to examine apoptosis of the retinal cells by TUNEL assay. RESULTS: Based on postoperative ultrasound findings, six of the eight rabbits had a greater degree of posterior vitreous detachment in the RGD eye compared to the fellow eye (p = 0.03). The total number and the average number of detached quadrants in the group of RGD peptide eyes was twenty-three and 2.85 respectively compared to seven and 0.85 for the control fellow eyes (p = 0.02). Scanning electron microscopy confirmed the presence of postoperative posterior vitreous detachment. There was no evidence of retinal cell apoptosis in RGD injected eyes. CONCLUSION: RGD peptide-assisted vitrectomy facilitated posterior vitreous detachment in rabbit eyes, suggesting that RGD-containing peptides may prove to be effective adjuncts in producing posterior vitreous separation during vitreous surgery.