The antimetastatic potential of a novel chemotherapeutic agent, alpha-difluoromethylornithine (DFMO), was evaluated in a murine model of intraocular melanoma. In vivo studies demonstrated that DFMO retarded the growth and spontaneous metastasis of murine intraocular melanomas. Further studies indicated that oral DFMO also exercised antimetastatic effects against the blood-borne stage of melanoma metastases. In vitro studies revealed that DFMO exerted impressive antiproliferative effects on three murine melanoma cell lines, four human cutaneous melanoma cell lines, one human uveal melanoma cell line, and one conjunctival melanoma cell line. DFMO inhibited in vitro DNA synthesis in human cutaneous melanoma cell lines by 84%-98% and that in two human ocular melanoma cell cultures by 62% and 86%, respectively. DFMO possesses several characteristics that render it an attractive chemotherapeutic agent for potential use in the management of uveal melanoma. These include its antiproliferative effect against a wide range of murine and human melanomas, its extremely low toxicity, and its ease of administration.