A 70-year-old patient with recurrent bilateral primary intraocular lymphoma (PIOL) was treated with local injections of methotrexate and periocular dexamethasone phosphate to both eyes over the course of 5 months. Local therapy consisted of a cycle to each eye of 3 intravitreal injections of methotrexate (200 microg in a total volume of 0.1 cc) administered on days 1, 5, and 8, followed by a subtenon injection of dexamethasone phosphate (7.5 mg in a total volume of 0.3 cc) on day 9. This treatment cycle was administered 4 times for the right eye and 3 times for the left eye, at 4 to 6 week intervals. Electroretinography was used to assess retinal function prior to and during each treatment regimen. Complete regression of the lymphomatous infiltrates and resolution of the vitritis was observed with preservation of visual acuity and no changes on electroretinography. The effect was sustained for 24 months after termination of treatment in the absence of systemic chemotherapy, radiation treatments, or maintenance intravitreal injections. Local combined chemotherapy can be used to treat recurrent PIOL, and can serve as successful palliative therapy in patients for whom further treatment with systemic chemotherapy or radiation is contraindicated.