We investigated whether there is an association between polymorphism of the CYP17 gene and rheumatoid arthritis in Chinese patients in central Taiwan. Genomic DNA was extracted from the peripheral blood of 146 female and 47 male RA patients, as well as from 42 female and 59 male control subjects; restriction fragment length polymorphism (defined as the A1 and A2 alleles) was then determined. Clinical variables such as rheumatoid factor positivity, extra-articular manifestations, and joint erosion were also investigated for the RA patients. We found that more male RA patients had the A1 allele (P=0.019) and fewer female RA patients the A2 allele than control subjects (P=0.048). In male RA patients, A1 carriers showed more extra-articular manifestations (P=0.048). In female patients, a significant decrease in A2 carriers mainly occurred in the later-onset age group (P=0.024). This study suggests that the A2 allele may significantly decrease the overall risk of developing RA. In women, the protective effect of A2 mainly affects the older age group. In men, the clinical severity of RA may decrease in patients with the A2/A2 genotype.