Abstract: Introduction: In a preliminary report to the 8'" International Congress on Behcet's Disease (BD) in 1998, we showed the efficacy of combination therapy with low dose pulse Cyclophosphamide (LDP) and Methotrexate (MTX) in posterior uveitis (PU) and retinal vasculitis (RV) of BD. We present here our experience with more patients and a longer follow up. Patients & Methods: BD Patients who were on the association of LDP and MTX due to PU and/or RV, and had received the drugs for more than 9 months, were selected for this evaluation. LDP was administered as 0.5 g/m2/body surface/month by intravenous infusion and MTX as 7.5 mg/week orally, as well as Prednisolone 0.5 mg/Kg/day orally. A disease activity index (DAI) based on the inflammatory state of each section of each eye, the visual acuity (VA), and a total adjusted DAI for each patient was calculated. Improvement and stabilization of the lesions were accepted as a good result. The comparison of these data before and after the treatment was made by the Student paired t test. Results: Thirty-nine patients with a mean follow up time of 18.2 months were evaluated. We had good result for PU in 84% of the eyes; the mean DAI decreased from 2.1 to 1.1 (p=0.00003). In RV the good result was seen in 77% of the eyes; the mean DAI decreased from 4.1 to 1.8 (p<0.00003). VA improved in 71% of the eyes; it increased from 4.1/10 to 5.1/10 by the Snellen chart (p<0.03). The total adjusted DAI improved in 90% of the patients. It decreased from 47.2 to 29.5 (p=0.000002). We compared these results with patients who have received LDP or MTX alone, with the same follow up time. In 168 patients receiving MTX the good results were as follow: 89% in PU, 83% in RV, 71% for VA and 71% for the total adjusted DAI. The good results in 123 patients receiving LDP was: 86% in PU, 77% in RV, 70% for VA and 72% for the total adjusted DAI. There was no statistical significant difference between these 3 methods for inflammatory indexes when taken alone, VA, and the rate of side effects. However, when all the indexes were put together (total adjusted DAI) LDP-MTX demonstrated its superiority to the other methods. Conclusion: Combination therapy with LDP and MTX in ocular lesions of BD was superior to the single therapy with the same drugs, by improving the total adjusted DAI. As this effect was not obvious in the short-term study, the advantage of this regimen may become more evident in the long-term outcome of ocular lesions.