Administration of Penicillin for Syphilis may lead to the Jarisch-Herxheimer reaction hours after treatment. Occurs due to lysis of spirochetes (so it can occur with Borrelia and Leptospirosis as well). The reaction is characterized by fever and chills.

The classical explanation of the Herxheimer reaction is that treatment results in the sudden death and destruction of large numbers of treponemes, with the liberation of protein products and toxins.