Intraocular and orbital malignant Schwannomas in two F344 rats are presented. The two Schwannomas were identified among approximately 60,000 male and 60,000 female F344 rats. The intraocular malignant Schwannoma occurred in the iris, invading the corneal stroma through the destroyed Descemet membrane. The malignant orbital Schwannoma occurred in the left orbit, invading the contralateral orbit along the optic nerve. Histologically, the intraocular Schwannoma consisted predominantly of a perivascular fascicular pattern of plump spindle cells associated with marked cytoplasmic vacuolization. The orbital Schwannoma consisted of Antoni type A and B pattern, but Antoni B tissues predominated. Antoni A tissues consisted of closely packed, elongated spindle cells arranged in interlacing fascicles, while Antoni B tissues were highly cellular and consisted of anaplastic, small cells associated with marked cyst formation. Immunohistochemically, the intraocular Schwannoma had a positive immunoreactivity for S-100 protein, while the orbital Schwannoma had a negative immunoreactivity. Ultrastructurally, the cells of both intraocular and orbital Schwannomas had long, thin cell processes and pericytoplasmic basal laminae. Particularly, the plump spindle cells of the intraocular Schwannoma were most strikingly characterized by the well developed, extremely attenuated cell processes arranged in a lamellar or spiral pattern. These cell processes and cell bodies were associated with numerous desmosomes. Intracytoplasmic filamentous granules and bodies, consisting of intermediate filaments approximately 7 nm in width, were additional characteristics of the plump spindle cells.