We evaluated the efficacy of intraocular and periocular fluorouracil treatment in an experimental iris tumor of the rabbit (Greene amelanotic melanoma). Four consecutive intravitreal injections of 1 mg of fluorouracil given twice weekly completely suppressed tumor growth in all treated eyes for six weeks if treatment was initiated 24 hours after tumor implantation. In contrast, all control eyes implanted with an equal number of Greene melanoma cells but treated with intravitreal saline developed massive tumor invasion of the iris within two weeks. Additional subconjunctival therapy following intravitreal therapy for two weeks was only slightly more effective than intravitreal therapy alone. If therapy was delayed for one week, the iris tumors became macroscopically visible and subsequent treatment with intravitreal and subconjunctival fluorouracil was of limited value in suppressing growth.