Thirty rabbits with established unilateral septic arthritis of the knee after inoculation with Staphylococcus aureus received cloxacillin 50 mg/kg x 2 i.m. and probenecid 250 mg x 1 p.o. from Day 3 to 21. In 26 knees, synovectomy was performed 3, 5, and 7 days after the inoculation, and four knees were not operated on. Further, synovectomy was performed in eight noninfected knees. The rabbits were killed 3 or 7 weeks after the operation, and the specimens were examined macroscopically and microscopically. All the cultures taken postoperatively and at killing were negative. Infected knees synovectomized on Day 3 differed, although marginally, 3 weeks postoperatively from the operated on, uninfected group; a minor loss of cartilage cellularity and glycosaminoglycans was observed, but there were no changes indicating arthrosis. At 7 weeks postoperatively, this difference was more pronounced. If synovectomy was performed at a later stage, increased destruction was observed: after 7 days of infection, all the knees presented cloning and vascular crossing of the tidemark, indicating arthrosis, which did not differ from those knees treated with only antibiotics. We conclude that synovectomy performed early in the course of infection may stop the destructive influence of enzymes and of the synovial membrane leading to irreversible changes in the cartilage.