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Current adjunctive therapies to glaucoma surgery have unreliable effects, are toxic, and have numerous late complications associated with their use. This study examined whether topical cyclosporin (CsA) prolongs bleb survival after glaucoma filtration surgery.Anesthetized white New Zealand rabbits underwent glaucoma filtration surgery with a drainage tube. Cyclosporin (2%), applied intraoperatively or as topical treatment following glaucoma filtration surgery, was compared with intraoperative mitomycin C (MMC) and an untreated control group.The bleb remained elevated for 15.1 ± 3.2 days in the untreated control group, 12.2 ± 2.1 days after intraoperative cyclosporin, and 27.5 ± 1.7 days after intraoperative mitomycin C (P< 0.001). When topical treatment with cyclosporin followed intraoperative mitomycin C, bleb survival significantly decreased to 19.2 ± 4.6 days (P= 0.003). Intraocular pressure (IOP) remained significantly reduced in the mitomycin C-treated group longer than in either the control or cyclosporine-treated groups.In comparison with mitomycin C, neither intraoperative nor postoperative treatment with cyclosporin was associated with a decrease in intraocular pressure or prolonged bleb survival. Contrary to the initial hypothesis, topical treatment with cyclosporin actually mitigated the beneficial effects of mitomycin C on bleb survival. Clinical implications of these findings for patients with functioning blebs deserve further study.