The antimetabolite 5-fluorouracil (5-FU) was used as adjunctive treatment in glaucomatous eyes with poor prognoses undergoing filtering surgery. By adjusting the frequency of postoperative 5-FU subconjunctival injections according to the clinical response, the author thought it might be possible to reduce episcleral fibroproliferation and maintain a patent filter while reducing complications. Sixty-three eyes underwent filtering surgery with subsequent subconjunctival injections of 5.0 to 7.5 mg 5-FU for 14 days. The antimetabolite was not administered if there was evidence of corneal toxicity as demonstrated by epithelial defects or filaments, flat anterior chamber, or a conjunctival wound leak. By adjusting the injections in this fashion, the total amount of 5-FU administered ranged between 17.5 and 62.5 mg (34.4 +/- 11.6 mg). After 1 year, successful surgical outcomes were observed in 13/15 eyes with aphakia (87%), 11/17 eyes with neovascular glaucoma (65%), 11/12 eyes with at least two previous failed filters (92%), and 5/6 eyes with inflammatory glaucoma (83%). Eyes with epithelial downgrowth and cicatrizing diseases of the conjunctiva also were treated. Overall, conjunctival wound leaks were observed in 24% of the eyes and 29% had detectable changes in their corneal epithelium with corneal defects and filaments. Although adjusting the dose of 5-FU appears to be safe and effective, this can be determined clearly only by a controlled randomized clinical trial.