We treated septic arthritis of the knee in 38 rabbits with cloxacillin i.m. once and twice daily combined with probenecid for 7 or 21 days, respectively, or with only cloxacillin i.m. thrice daily for 7 days. The animals were killed weekly in groups up to 5 weeks after inoculation. Aspirated cultures obtained after 4 days of treatment were always negative. Histologic specimens revealed progressive joint destruction, but at a slower rate after frequent treatment independent of the period. We concluded that antibiotic therapy alone could not prevent destruction of articular cartilage once bacterial arthritis was established.