Aim-To develop and assess a protocol for the treatment of intraocular lymphoma by intravitreal injection of methotrexate and thiotepa. Methods-A patient with intraocular nonHodgkin's lymphoma which recurred after radiotherapy and repeated systemic chemotherapeutic regimens underwent repeated intravitreal injections of methotrexate and thiotepa. The patient was closely monitored by cytology, anterior chamber flare measurements, IL-10 and IL-6 levels. Methotrexate drug clearance studies were performed on vitreous samples taken before each injection. Results-Complete tumour clearance was achieved by the third week of therapy. IL-10 and IL-6 levels quickly dropped to barely detectable levels as the tumour was cleared from the eye. Flare measurements decreased from 500 to 15 photons/s over the same time. A plot of the methotrexate levels over time revealed a first order kinetic rate of elimination with an eVective tumoricidal intravitreal dose persisting for 5 days after injection. Conclusion-Intravitreal chemotherapy for the treatment of recurrent intraocular lymphoma appears eVective in prolonging local remission of ocular disease even in the presence of an aggressively growing tumour. A single intravitreal injection of methotrexate can lead to a prolonged tumoricidal concentration lasting for a longer period than that achieved by systemic administration. (Br J Ophthalmol 1999;83:448-451) Primary central nervous system (CNS) and intraocular non-Hodgkin's lymphoma (NHL) is initially treated with systemic chemotherapy administered alone or in combination with radiotherapy.