In joints with bacterial arthritis, continuing prolonged destruction of cartilage may occur in spite of prompt, effective antibiotic therapy. We measured the extent to which early antibiotic therapy with ceforanide altered the degradation of the cartilage after arthritis due to Staphylococcus aureus had been produced in the knee joint in rabbits. Degradation of the cartilage was quantified by analyses for glycosaminoglycan and collagen. Three weeks after the infection was produced, the cartilage had lost more than half of its glycosaminoglycan whether the antibiotic therapy had been started at one, two, or seven days after infection. Beginning the antibiotic treatment one day after infection reduced over-all loss of collagen by 37 per cent and decreased the area of erosion of the infected articular surfaces. When antibiotic treatment was begun at four, eight, or twelve hours after infection, the loss of glycosaminoglycan averaged 18 per cent. Prophylaxis with antibiotics completely prevented any degradation of the cartilage. Clinical relevance: The findings reported here show how rapidly cartilage loses glycosaminoglycan when it is involved by arthritis caused by staphylococci and how early treatment of the infection reduces the loss of collagen. There is less protection against loss of glycosaminoglycan. The results emphasize the need for early diagnosis and treatment of infectious synovitis and support the rationale for early administration of antibiotics without waiting for identification of the responsible bacteria.