Genetic background is important in determining whether certain infecting bacteria disseminate to the joint and cause arthritis. We assessed whetherAPOEgenotype is associated with the presence of DNA fromChlamydiaor other bacteria in synovial tissues of patients with various arthritides. Nucleic acids from synovial tissues of 135 patients were screened by PCR for DNA fromChlamydia trachomatis,C. pneumoniaeand other bacteria (pan-bacteria).APOEgenotype was determined by a PCR-based method for all patients in each of four resulting groups comprised of about 35 individuals each, positive forC. trachomatisonly,C. pneumoniaeonly, other bacteria, or no bacteria. RT-PCR was used to assess synovialAPOEexpression. The latter assays confirmed thatAPOEmRNA is present in synovial tissue. Determination ofAPOEgenotype showed that patients PCR-negative in all assays, and those positive in theC. trachomatis- and pan-bacteria- (excludingChlamydia) directed assays, had distributions of theAPOEϵ2, ϵ3 and ϵ4 alleles mirroring those of the general population (i.e. about 8%, 79% and 13%, respectively). In contrast, 68% of patients withC. pneumoniaeDNA in synovium possessed a copy of the ϵ4 allele. These results indicate that no association exists betweenAPOEgenotype and synovial presence ofC. trachomatisor other bacteria. However, individuals bearing at least one copy of theAPOEϵ4 allele may be at increased risk for synovial infection byC. pneumoniae.