t CD4 is a candidate gene in autoimmune diseases, including rheumatoid arthritis (RA). Because the CD4 receptor is crucial for appropriate antigen responses of CD4? T cells, changes in CD4 expression and CD4? T-cell activity may influence tolerance or tissue destruction in autoimmune diseases and contribute to their risk. We analyzed two polymorphisms of the CD4 in 172 female Egyptian patients with RA and in 112 matched healthy control. Genotyping of CD4-11743 and CD4-10845 was determined by restriction fragment length polymorphismpolymerase chain reaction (PCR–RFLP). Subjects with the CC genotype of CD4-11743 were significantly more likely to develop RA (OR = 2.7, P = 0.03) and more likely to have sever RA (OR = 2.7, P = 0.024). Carrier of A allele of CD4-10845 was significantly more likely to develop sever RA (OR = 3.7, P = 0.000). CD4-11743 genetic polymorphisms are associated with the susceptibility and severity of RA, and CD4-10845 genetic polymorphisms are associated with the severity of RA. Keywords CD4  Gene  Polymorphism  Rheumatoid arthritis