To investigate the role of tumor necrosis factor receptor 2 microsatellite allele (TNFR2ms) and TNFR2 exon 6 polymorphisms in the pathogenesis of rheumatoid arthritis (RA) in Taiwan. Methods. TNFR2ms was determined in 114 patients with RA and 75 healthy controls by polymerase chain reaction (PCR) method and electrophoresis with sequencing gel. The TNFR2 exon 6 polymorphisms were also simultaneously measured by PCR restriction fragment length polymorphism method.The phenotypic and allelic frequencies of TNFR2ms 18 were significantly lower in patients with RA than in controls. The genotype frequency of TNFR2ms 16/18 was also significantly decreased in patients. In contrast, the phenotypic and allelic frequencies of TNFR2ms 15 showed a trend to be increased in patients with RA. There were no significant differences in the frequencies of various TNFR2ms and exon 6 polymorphisms concerning presence and absence of rheumatoid factor, bone erosion, rheumatoid nodules, or Sjögren's syndrome manifestation. Conclusion. TNFR2ms 18 may have a protective effect on the development of RA in Taiwanese, while TNFR2ms 15 tends to have a precipitating effect. TNFR2 exon 6 polymorphisms are not related to susceptibility for RA. TNFR2ms and exon 6 polymorphisms were not associated with the clinical manifestations of RA in Taiwanese. A synergistic effect for susceptibility to RA was found between TNFR2ms 15 and HLA-DR4.