Nickel subsulfide, alpha Ni3S2, was administered to albino Fischer rats by a single injection into the vitreous body of the right eye (0.5 mg alpha Ni3S2/rat, suspended in 20 microliter of NaCl vehicle). Control rats received a similar injection of the vehicle. Malignant tumors developed in the injected eyes of 14/15 alpha Ni3S2-treated rats by 8 months (vs. 0/11 controls, p less than 0.001). Five of the injected eyes of alpha Ni3S2-treated rats contained multiple tumors. The 21 eye tumors that were induced by alpha Ni3S2 included 11 melanomas, four retinoblastomas, three gliomas, and three unclassified malignant neoplasms. Three of the melanomas developed extraocular extensions; one of the melanomas metastasized to lungs and brain. Although the melanomas arose from amelanotic uveal melanocytes, melanosomes were observed in electron micrographs of the tumor cells. This study provides a new experimental model for chemical induction of ocular neoplasms. As a procedure to test the carcinogenicity of nickel compounds, intraocular injection has the advantages of short latency period, high tumor incidence, and ease of tumor detection.