Ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one), a synthetic heterocyclic seleno-organic compound, has been shown to act as a scavenger of reactive oxygen species (ROS). We have previously reported that interleukin-1 (IL-1) inhibited proteoglycan (PG) synthesis and induced the production of ROS in cartilage explants and isolated chondrocyte cultures. In this study, we report the protective effect of ebselen against IL-1-mediated inhibition of PG synthesis and ROS induction in cultured cartilage explants and chondrocytes. Ebselen also reversed the inhibition of PG synthesis in mechanically stressed cultured chondrocytes. These data suggest that the use of the antioxidant ebselen may be a useful tool for studying the mechanisms of cartilage degradation.