A genetic system for activating or inactivating genes specifically in joint tissues would be particularly useful for further studies of joint formation and maintenance. Here we take advantage of the tissue-specific expression pattern of the Gdf5 gene to engineer a Cre/loxP system (Nagy 2000), Gdf5-Cre, that can be used to remove or ectopically express genes in joints. Tests with reporter mice show that this system is capable of modifying genes in all of the structures of the mature synovial joint, including the ligaments of the joint capsule, the synovial membrane, and the articular cartilage. Gdf5-Cre recombination bypasses the early embryonic lethality of null mutations in Bmpr1a, and shows that this receptor is required for early joint formation at some locations and for initiation of programmed cell death in webbing between digits. Interestingly, Bmpr1a is also required for postnatal maintenance of articular cartilage throughout most of the skeleton. In Gdf5-Cre/Bmpr1afloxP mice, articular cartilage initially forms normally, but subsequently loses expression of several key cartilage markers after birth. It ultimately fibrillates and degenerates, resulting in severe osteoarthritis and loss of mobility. These experiments suggest that BMP signaling is required for normal maintenance of postnatal articular cartilage, and that modulation of the BMP signaling pathway may play an important role in joint disease.