The effect of subconjunctival interferon-alpha-2b treatment on success rates after glaucoma filtering surgery was compared with that of 5-fluorouracil in a pilot study. Surgery was defined as successful if it reduced the intraocular pressure to less than 21 mm Hg without medication. Initially, doses of 2 x 10 IU of interferon-alpha were given. By 6 months postoperatively, 6 of 16 interferon-treated patients had had to resume medication to control their glaucoma, compared with only 2 of 16 patients treated with 5-fluorouracil (p = 0.08). When the dose of interferon was increased to 1 x 10 IU, 2 of 13 interferon-treated patients had to resume by 6 months (p = 0.14 when compared with the patients receiving the lower dose). Corneal epithelial defects were less common in the 1 x 10 IU interferon-alpha group compared with the 5-fluorouracil group (1 of 13 vs. 11 of 16; p = 0.0002) while other side effects, both local and systemic, were similar between the two groups. This study shows that (a) interferon-alpha-2b, in the doses used, is well-tolerated by the human eye, and (b) interferon-alpha-2b may reduce the risk of failure of glaucoma filtration surgery with fewer corneal complications than are seen with 5-fluorouracil.