Inbred mice infected intravenously with Mycoplasma pulmonis develop a severe and persistent arthritis. Maximal severity of the arthritis is reached 10 to 14 days postinfection, and in some animals, ian arthritic condition subsequently persists throughout life. Chemotherapy was given either at the time of infection or during the acute phase of the disease. Tobramycin, gentamicin, and, to a lesser extent, kanamycin delayed the development of arthritis when administered at the time of infection, and, when given therapeutically, they all reduced inflammation and swelling of arthritic joints. Recovery of the mycoplasma was lowest from the joints of more treated with tobramycin or gentamicin, indicating that these two antibiotics were mycoplasmacidal and that the remission of arthritis was correlated with the eradication of the organisms.