Polymorphism (variable number of tandem repeats) in the second intron of the interleukin-1 receptor antagonist (IL-1Ra) gene and two single nucleotide polymorphisms at positions -511 and +3954 of the IL-1beta gene may be associated with an increased risk of rheumatoid arthritis (RA). This study used sex stratification to investigate a correlation of the three genetic polymorphisms with the risk of RA, on patients with RA and healthy controls. Polymerase chain reaction (PCR) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) were performed. The frequencies of the IL-1beta+3954 allele and genotype in female patients were significantly different compared with the controls; but in males, only the frequency of the IL-1beta+3954 allele was different. The frequency of the IL-1RN genotype in patients was not statistically different compared with the controls; however, the frequency of IL-1RN allele in female patients was different. The association of the three polymorphisms with the susceptibility to RA appears to be significantly affected by gender.