The purpose of this study was to investigate the possible association between estrogen receptor alpha (ERalpha) polymorphism and pain susceptibility in female symptomatic temporomandibular joint (TMJ) osteoarthritis (OA) patients. A patient group of 100 women, diagnosed as TMJ OA according to the research diagnostic criteria for temporomandibular disorders, were selected, and 74 women with no signs and symptoms of temporomandibular disorder were assigned to a control group. Pvu II and Xba I restriction fragment length polymorphisms were analyzed by direct haplotyping. The patient group was divided into three subgroups according to a visual analog scale (VAS): mild pain (0<or=VAS<4); moderate pain (4<or=VAS<7); severe pain (7<or=VAS<or=10). Frequencies of genotypes and haplotypes in the patient and control groups were compared, and the association between pain intensity and copy numbers of PX haplotype were evaluated using the chi-square test. No significant differences in genotype and haplotype frequencies were observed between the patient and control groups (p>.05). TMJ OA patients carrying the PX haplotype were found to have a significantly higher risk of moderate or severe pain compared to those without the PX haplotype, suggesting that ERalpha polymorphism may be associated with pain susceptibility in female TMJ OA patients.