The use of one intraoperative application of mitomycin C at the filtration site has been effective in eyes at increased risk for failure of routine trabeculectomy. To study the efficacy and safety of this technique in patients with refractory glaucoma, we prospectively examined 30 eyes of 26 black patients in whom a 0.2-mg/ml solution of mitomycin C was applied between Tenon's capsule and the sclera for five minutes before trabeculectomy. The results were compared to those found in a matched group of 30 eyes of 28 patients who underwent trabeculectomy without mitomycin C. The mean postoperative intraocular pressures were significantly lower in the mitomycin C group than in the control group (P = .001). Of the 30 eyes in the mitomycin C group, 25 (83%) had an intraocular pressure of less than 21 mm Hg without glaucoma medication, compared to 11 of 30 (37%) in the control group (P = .00006). In the mitomycin C group, 19 eyes (63%) developed a cystic avascular thin-walled filtering bleb, four eyes (13%) a late positive Seidel test, and one eye slight scleral thinning over the area where the mitomycin C was applied. Although mitomycin C is effective when used in this manner, further study is required to determine the long-term complications.