The aim of this study was to investigate the effect of a third generation bisphosphonate (CGP 42'446) on the bone and cartilage of the knee in a rabbit model of inflammatory arthritis (carrageenin arthritis model). Mature female New Zealand white rabbits were divided into two groups, control (n=7) or experimental (n=8). Both groups received 7 intra-articular injections of 0.3 ml of 1% carrageenin solution in the right knee and 0.3 ml of saline in the left knee over a 4 week period. The experimental group in addition received 10 μg/kg of bisphosphonate subcutaneously 3 times/week for 4 weeks. Upon sacrifice, the left and right femurs and tibiae from all the rabbits were excised. Both decalcified and undecalcified sections from the femoral condyles and the tibial plateau were examined by light microscopy and histomorphometry.Microscopically, the injected knees in the control group showed changes of inflammatory arthritis with pannus formation and resorption of articular cartilage when compared to the contralateral leg. The remaining cartilage showed fibrillation and extensive chondrocyte necrosis. Safranin O staining demonstrated loss of proteoglycans. Thinning of subchondral bone was seen focally. Vascular penetration of the calcified cartilage was a variable feature. Treatment with bisphosphonate affected the inflammatory component as there was decreased cartilage erosion and pannus formation. Bisphosphonate treatment also appeared to limit the subchondral bone loss.