The chondroprotective effect of betamethasone was examined to determine if corticosteroids can decrease articular cartilage injury caused by inflammatory exudate in Staphylococcus aureus gonarthritis in rabbits. Three experimental groups of antibiotic-treated rabbits were created, comparing parenteral versus low-dose intraarticular routes of betamethasone administration. Rabbits that received ceftriaxone plus supplemental parenteral betamethasone (group 2) demonstrated significantly less articular cartilage proteoglycan loss than did rabbits treated with antibiotics alone (group 1). Supplemental intraarticular betamethasone (group 3) was somewhat less effective in this regard, possibly reflecting the smaller steroid dosage. This animal study introduces histologic and biochemical evidence that betamethasone, administered early and in conjunction with appropriate systemic antibiotics, may help protect infected articular cartilage from proteolytic degradation. Further study is needed to prove safety and efficacy of corticosteroids before recommending their clinical use in the treatment of septic arthritis.