Reactive arthritis, previously known as Reiter's syndrome, is a form of inflammatory arthritis that develops in response to an infection in another part of the body (cross-reactivity). Coming into contact with bacteria and developing an infection can trigger the disease. By the time a person presents with symptoms, the "trigger" infection has often been cured or is in remission in chronic cases, thus making determination of the initial cause difficult.

The manifestations of reactive arthritis include the following triad of symptoms: inflammatory arthritis of large joints, inflammation of the eyes in the form of conjunctivitis or uveitis, and urethritis in men or cervicitis in women. Arthritis occurring alone following sexual exposure or enteric infection is also known as reactive arthritis. Affected people may present with mucocutaneous lesions, as well as psoriasis-like skin lesions such as circinate balanitis, and keratoderma blennorrhagicum. Enthesitis can involve the Achilles tendon resulting in heel pain. Not all affected persons have all the manifestations.

The clinical pattern of reactive arthritis commonly consists of an inflammation of fewer than five joints which often includes the knee or sacroiliac joint. The arthritis may be "additive" (more joints become inflamed in addition to the primarily affected one) or "migratory" (new joints become inflamed after the initially inflamed site has already improved).

As a seronegative spondyloarthropathy, laboratory analysis of blood will show that the patient is rheumatoid factor negative and often HLA-B27 positive. The most common triggers are intestinal infections (with Salmonella, Shigella or Campylobacter) and sexually transmitted infections (with Chlamydia trachomatis); however, it also can happen after group A streptococcal infections.

It most commonly strikes individuals aged 20–40 years of age, is more common in men than in women, and is more common in white than in black people. This is owing to the high frequency of the HLA-B27 gene in the white population. It can occur in epidemic form. Patients with HIV have an increased risk of developing reactive arthritis as well.

Numerous cases during World Wars I and II focused attention on the triad of arthritis, urethritis, and conjunctivitis (often with additional mucocutaneous lesions), which at that time was also referred to as Fiessenger–Leroy–Reiter syndrome.

Reactive arthritis is associated with the HLA-B27 gene on chromosome 6 and by the presence of enthesitis as the basic pathologic lesion and is triggered by a preceding infection. The most common triggering infection in the US is a genital infection with Chlamydia trachomatis. Other bacteria known to cause reactive arthritis which are more common worldwide are Ureaplasma urealyticum, Salmonella spp., Shigella spp., Yersinia spp., and Campylobacter spp. A bout of food poisoning or a gastrointestinal infection may also precede the disease (the last four genera of bacteria mentioned above are enteric bacteria). Shigella is the most common organism causing reactive arthritis following diarrhea. Chlamydia trachomatis is the most common cause of reactive arthritis following urethritis. Ureaplasma and mycoplasma are rare causes. There is some circumstantial evidence for other organisms causing the disease, but the details are unclear.

Reactive arthritis usually manifests about 1–3 weeks after a known infection. The mechanism of interaction between the infecting organism and the host is unknown. Synovial fluid cultures are negative, suggesting that reactive arthritis is caused either by an autoimmune response involving cross-reactivity of bacterial antigens with joint tissues or by bacterial antigens that have somehow become deposited in the joints.^{[citation needed]}