We studied the effect of ethacrynic acid on intraocular pressure in eyes with advanced open-angle glaucoma. Five to 15 microliters of ethacrynic acid (3.3 to 9.8 micrograms) was injected intracamerally after retrobulbar anesthesia was achieved in five eyes of five patients with advanced glaucoma. Intraocular pressure before treatment ranged from 26 to 46 mm Hg with maximal medical treatment. A reduction in intraocular pressure from 9 to 31 mm Hg was observed in all patients three to 24 hours after treatment, and this effect lasted for three days, with a gradual return of intraocular pressure to pretreatment values one week after treatment. No acute corneal or anterior chamber side effects were observed and results of corneal endothelial cells counts were essentially unchanged two months after treatment. We suggest that ethacrynic acid may represent a new class of antiglaucoma medication. Intracameral administration of ethacrynic acid or a derivative might be contemplated in the future at the time of other ocular surgical procedures to treat short-term intraocular pressure increase.