Indocyanine green (ICG)-enhanced laser therapy was evaluated for the treatment of experimental intraocular melanoma. Immediately after an intravenous injection of ICG, a 790-nm chromophore, 810-nm semiconductor diode laser was used to irradiate Greene hamster melanomas that had been implanted in the iris of rabbits. ICG-enhanced laser treatment of melanoma (14 eyes) was compared with treatment by laser alone (4 eyes), ICG alone (1 eye), and no treatment (2 eyes). Tumors treated with ICG-enhanced laser showed no growth after treatment, as judged by clinical examination and photography. Histologically, 4 of the 14 tumors treated with ICG-enhanced laser showed total necrosis, whereas the remaining 10 tumors treated similarly demonstrated only rare viable cells around blood vessels or at the tumor periphery. Laser treatment without ICG enhancement resulted in only superficial tumor necrosis, and all four of these tumors continued to grow after treatment. With further evaluation, indocyanine green in combination with a commercially available diode laser may be useful in the treatment of ocular melanoma.