Rheumatoid arthritis (RA) is a systemic chronic inflammatorydisease of the joints. Systemic lupus erythematosus (SLE) is anautoimmune disease which has the potential to involve multiple organs.There are several lines of evidence that chemokines play an importantrole in the inflammatory development and progression of autoimmunediseases. RANTES is a chemokine that is member of the CC chemokines.The aim of the work was to evaluate the possible effect of theRANTES gene on the susceptibility to RA and SLE by examining thepolymorphism of promoter at position -403 of this gene in RA and SLEpatients and ethnically matched controls.Subjects and methods: The study included 32 rheumatoid arthritispatients and 32 systemic lupus erythematosus patients .Thirty sex andage matched healthy individuals were also included in the study as acontrol group. All patients were subjected to: careful history taking,assessment of disease activity, laboratory investigations as well asRANTES-403 genotyping by PCR-RFLP.Results: RANTES -403 A/A genotype frequency was significantlyhigher in RA (18.75%) and SLE (15.63 %) in comparison to healthyindividuals (0%) (p=0.038 and p=0.037 respectively). However, Nosignificant association was found between clinical aspects and RANTESpolymorphism.Conclusion: These findings suggest that the presence of the Aallele in position -403 in the RANTES gene may be a possible risk factorin the pathogenesis of SLE and RA .The use of RANTES gene therapy appears to be a promising lineof treatment for RA and SLE patients.