Synovial fluid analysis may be ordered to help diagnose the cause of joint inflammation, pain, swelling, and fluid accumulation. Diseases and conditions affecting one or more joints and the synovial fluid can be divided into four main categories:

• Infectious diseases – those caused by bacteria, fungi, or viruses. They may originate in the joint or spread there from other places in the body. These conditions include acute and chronic septic arthritis.
• Bleeding – bleeding disorders and/or joint injury can lead to blood in the synovial fluid. This is commonly present in people with untreated blood clotting disorders such as hemophilia or von Willebrand disease.
• Inflammatory diseases –
• Conditions that cause crystal formation and accumulation such as gout (needle-like uric acid crystals) and pseudogout (calcium pyrophosphate dihydrate crystals). These typically affect the feet and legs.
• Conditions that cause joint inflammation, such as synovitis, or other immune responses. These may include autoimmune disorders such as rheumatoid arthritis and lupus.
• Degenerative diseases – such as osteoarthritis

Synovial fluid analysis may be ordered when a healthcare practitioner suspects that a person has a condition or disease involving one or more of their joints. It may be ordered when someone has some combination of the following signs and symptoms:

• Joint pain
• Redness over the joint
• Joint inflammation and swelling
• Synovial fluid accumulation

It may sometimes be ordered to monitor a person with a known joint condition.

Synovial fluid usually contains a small amount of glucose and protein and may have a few white blood cells (WBCs) and red blood cells (RBCs).

There are a variety of joint abnormalities, including osteoarthritis, rheumatoid arthritis, gout, and infection (septic arthritis), that can cause inflammation, swelling, an accumulation of synovial fluid, and sometimes bleeding into one or more joints. These conditions can limit mobility and, if left untreated, may permanently damage the joints.

Results of tests performed on a sample of synovial fluid may include:

Physical characteristics – the normal appearance of a sample of synovial fluid is usually:

• Straw colored
• Clear
• Moderately viscous – drops of it from a syringe needle will form a "string" a few inches long.

Changes in the physical characteristics may provide clues to the disease present, such as:

• Less viscous fluid may be seen with inflammation.
• Cloudy synovial fluid may indicate the presence of microbes, white blood cells, or crystals.
• Reddish synovial fluid may indicate the presence of blood, but an increased number of red blood cells may also be present in cloudy synovial fluid.

An individual's joint may be affected by more than one of these physical changes at a time.

Chemical tests – tests that may be performed on synovial fluid samples include:

• Glucose—typically a bit lower than blood glucose levels; may be significantly lower with joint inflammation and infection.
• Protein—increased with bacterial infection
• Uric acid—increased with gout

Microscopic examination – Normal synovial fluid has small numbers of white blood cells (WBCs) and red blood cells (RBCs) but no microbes or crystals present. Laboratories may examine drops of the synovial fluid and/or use a special centrifuge (cytocentrifuge) to concentrate the fluid's cells at the bottom of a test tube. Samples are placed on a slide, treated with special stain, and an evaluation of the different kinds of cells present is performed.

• Total cell counts—number of WBCs and RBCs in the sample; increased WBCs may be seen with infections and with conditions such as gout and rheumatoid arthritis.
• A WBC differential determines the percentages of different types of WBCs. An increased number of neutrophils may be seen with bacterial infections. Greater than 2% eosinophils may suggest Lyme disease, parasitic arthritis, rheumatoid disease, or tubercular arthritis.
• Synovial fluid is evaluated under polarized light to recognize the presence of crystals and to distinguish the types of crystals that are present. Needle-like monosodium urate crystals are associated with gout and calcium pyrophosphate crystals are associated with pseudogout.

Infectious disease tests – in addition to chemistry tests, other tests may be performed to look for microbes if infection is suspected.

• Gram stain allows for the direct observation of bacteria or fungi under a microscope. There should be no microbes present in synovial fluid.
• Culture and susceptibility testing is ordered to determine what type of microbes are present. If bacteria are present, susceptibility testing against certain antibiotics can be performed to guide antimicrobial therapy. If there are no microbes present, it does not rule out an infection; they may be present in small numbers or their growth may be inhibited because of prior antibiotic therapy.
• Other tests for infectious diseases that are less commonly ordered include AFB testing. This test for the presence of mycobacteria may help diagnose tuberculosis. Molecular test methods for Mycobacteria tuberculosis are more sensitive and specific than traditional cultures and may also be performed.

A blood or urine uric acid or blood glucose test may be ordered to compare concentrations with those in the synovial fluid. If a healthcare practitioner suspects that an individual has a systemic infection, then a blood culture may be ordered in addition to the synovial fluid analysis.

Joint injury, surgery, and joint replacement can increase the risk of developing an infection in a joint.