Although corticosteroids remain the mainstay of therapy for intraocular inflammation, many patients are intolerant or resistant to corticosteroid therapy. In these patients, other immunosuppressive agents have been employed to control potentially sight-threatening uveitis. Nevertheless, ideal therapy for these patients remains elusive, and there is a need for new immunosuppressive agents with varying modes of action and side effect profiles. Leflunomide, an isoxazole derivative, has profound immunosuppressive activity. Leflunomide inhibits autoimmune disease in animal models and has been used to treat patients with rheumatoid arthritis (RA). We propose a randomized masked pilot trial of leflunomide versus placebo for the treatment of uveitis. Sixteen patients 16 years of age or older with active intermediate, posterior, or panuveitis will be randomly assigned to receive prednisone and leflunomide or prednisone and placebo. Patients will then have the prednisone tapered according to a standardized schedule. The primary purpose of the study is to investigate the safety and efficacy of leflunomide versus placebo. The primary safety endpoint is the frequency of any of the following: abdominal pain, diarrhea, skin rash, hypertension, and alopecia. In addition, weight loss distributions and change in liver function tests will be described. The primary efficacy endpoint is any one or more of the following (1) a decrease of 10 or more letters in visual acuity from the baseline score for any reason, or (2) inability to taper prednisone to 10 mg qd by week 16 post randomization, or (3) inability to maintain the prednisone taper through Month 6 or Month 12, or (4) the addition of systemic therapy to treat ocular inflammatory disease. Secondary outcomes will include change in vitreous haze and presence or absence of cystoid macular edema.