Two common STDs are treated with a shot in the buttocks: syphilis and gonorrhea. Both require an intramuscular injection, typically given in the upper outer area of the gluteal muscle, because the medications need to be delivered deep into a large muscle for proper absorption. Syphilis is the one most associated with this treatment, as the injection is the only first-line option. Gonorrhea also requires an injectable antibiotic, though the volume is smaller and the shot is quicker.
Syphilis: The Classic Buttocks Injection
Syphilis is treated with a long-acting form of penicillin that can only be given as an intramuscular injection. There is no pill alternative for this one. For primary or secondary syphilis (the earlier stages), you receive a single shot of 2.4 million units of the medication. That sounds like a lot, and it is a thick, slow-moving injection. The full dose comes in about 2 milliliters of fluid that the nurse injects slowly, roughly one milliliter every 10 seconds, to give the muscle time to absorb it.
The reason this particular antibiotic works so well is that it releases penicillin gradually into your bloodstream over weeks. A single dose maintains detectable levels in the blood for up to four weeks. That slow release is what makes it effective against the syphilis bacterium, which reproduces slowly and needs sustained antibiotic exposure to be eliminated.
If syphilis has progressed to later stages (latent syphilis that has been present for more than a year), the treatment involves the same injection given once per week for three consecutive weeks. Each visit is the same 2.4 million unit dose in the buttock.
Gonorrhea: A Smaller, Faster Shot
Gonorrhea is treated with a single intramuscular injection of a different antibiotic, a type of cephalosporin. The standard dose is 500 mg for most people. This injection treats gonorrhea infections of the throat, genitals, and rectum alike. The volume of fluid is smaller than the syphilis shot, so the injection itself is faster and generally less uncomfortable.
Gonorrhea requires an injectable antibiotic rather than a pill because the bacterium has developed significant resistance to oral antibiotics over the years. The intramuscular route delivers a high, reliable concentration of the drug directly into the bloodstream, which is more effective at clearing the infection in a single visit.
Why the Buttocks Specifically
These injections go into the gluteal muscles because they are the largest muscles in the body and can accommodate the volume of fluid involved. This is especially important for the syphilis shot, which is a thick, viscous liquid that would cause significant pain or even abscesses if injected into a smaller muscle like the deltoid in your arm.
The preferred injection site is the ventrogluteal area, which is the upper outer portion of your hip and buttock. This spot is chosen over the center of the buttock because it sits farther from the sciatic nerve and major blood vessels, reducing the risk of complications. You’ll typically be asked to lie on your side or stand with your weight shifted to the opposite leg.
What the Injection Feels Like
The gonorrhea shot is relatively quick and feels like most other injections, with brief stinging at the site. Soreness at the injection spot for a day or two is common but mild.
The syphilis injection is a different experience. The medication is notably thick, and the slow injection process means the needle stays in the muscle for 20 to 30 seconds. Many clinics mix a small amount of a local anesthetic (lidocaine) into the syringe to reduce pain during the injection. Even so, most people describe it as uncomfortable, with a deep aching or burning sensation during and after the shot. Soreness at the injection site can last a few days. Walking around and gently stretching the muscle afterward can help.
One reaction specific to syphilis treatment is worth knowing about. Within a few hours of receiving the shot, some people develop fever, chills, headache, muscle pain, or a worsening of any existing rash. This is called a Herxheimer reaction, and it happens because the rapid die-off of syphilis bacteria triggers a temporary inflammatory response. It typically resolves within 24 hours on its own and is not an allergic reaction. Over-the-counter fever reducers can help manage the symptoms.
After the Shot: What to Expect
For both syphilis and gonorrhea, you should avoid sexual activity for at least seven days after receiving a single-dose injection. This gives the antibiotic time to fully clear the infection so you don’t pass it to a partner.
Gonorrhea treatment is typically one and done. You may be asked to return for a follow-up test a few weeks later to confirm the infection has cleared, especially for throat infections, which can be harder to treat.
Syphilis requires blood tests at regular intervals after treatment (usually at 6 and 12 months) to confirm that antibody levels are dropping as expected. The injection cures the infection, but your doctor needs to verify the response through these follow-up labs. If you were treated for late-stage syphilis with three weekly injections, completing all three is essential. Missing a dose can allow the bacterium to survive.
What About Other STDs
Most other STDs are treated with oral medications. Chlamydia is treated with antibiotic pills. Herpes and HIV are managed with daily oral medications. Trichomoniasis is treated with a single oral dose of an antibiotic. The buttocks injection is specifically associated with syphilis and gonorrhea because of the unique properties of the antibiotics that work against those particular bacteria.