To investigate the role of manganese superoxide dismutase (MnSOD) and cytochrome P450 1A1 (CYP1A1) gene polymorphisms in the pathogenesis of rheumatoid arthritis (RA) in Taiwan, MnSOD and CYP1A1 genes polymorphisms were determined by he polymerase chain reaction/restriction fragment length polymorphism method in 112 patients with RA and 96 controls. There were no significant differences in the genotype, allele, and phenotype frequencies of MnSOD Ala-9Val (C1183T) polymorphisms between patients with RA and controls. The polymorphism of MnSOD 5777T, threonine at the 58th amino acid, cannot be found in RA patients and controls in Taiwan. The allele and phenotype frequencies of CYP1A1 4887A and genotype frequency of CYP1A1 4887C/A were lower in RA patients than in controls, whereas the significant difference was lost after correction. MnSOD C1183T polymorphisms were not associated with the clinical manifestations of RA. However, RA patients with CYP1A1 4889G/G have significantly higher frequency of Sjögren's syndrome, especially in the presence of MnSOD 1183T/T. Patients with CYP1A1 4887C/A also have a trend to develop Sjögren's syndrome in the presence of MnSOD 1183T/T. The linkage disequilibrium between CYP1A1 4889G and CYP1A1 6235C can be found in this study. MnSOD gene polymorphisms are not related to susceptibility to RA in Taiwan, whereas individuals with CYP1A1 4887A tend to avoid the development of RA. Moreover, CYP1A1 4889G/G and 4887C/A may play a role in the development of Sjögren's syndrome, especially in the presence of MnSOD 1183T/T. These findings are preliminary. A further confirmation study is necessary.