The course of hindpaw arthropathy induced by single intradermal tail injections of sonicated, extensively-o-acetylated peptidoglycan (S-o-PG) from Neisseria gonorrhoeae was studied in male Lewis rats. Following a latent period of approximately 2 weeks, the hindpaw skin became inflamed and the ankles and hindfeet became swollen. Swelling was greatest at 32 days after injection, and decreased somewhat by day 40 to a level which remained well above normal. An aggressive, acute arthritis accompanied the swelling through day 24. The main features of the arthritis included the infiltration of periarticular tissues by many neutrophils, pannus formation, and the erosion of cartilage and subchondral bone. By day 32 the process had progressed and chronic inflammatory changes were becoming superimposed upon the acute changes. By day 40, chronic inflammatory changes predominated and fibrous ankylosis were established. In addition to the arthritis, deposition and absorption of bone occurred on surfaces unrelated to joints (e.g., the tibial shaft and plantar surface of the calcaneum), while tendons about the ankle developed adhesions following a severe tenosynovitis. This study supports the notion that cell-wall components may trigger severe arthropathy even in the absence of viable intraarticular gonococci.