Calpain II, a high Ca 2 + -requiring form of Ca 2 + -dependent cysteine proteinase (EC 3.4.22.17), isolated from bovine lens was found to cleave actin and vimentin, two major cytoskeletal elements of the lens. Polyacrylamide gel electrophoresis revealed that actin (M r 43000) was broken down through intermediary products of approximate M r 42000 and 40000, while vimentin (M r 57000) was rapidly cleaved into several fragments ranging from M r 44000 to 20000. The cleavage was dependent on Ca 2 + and could be blocked by calpastatin, a calpain-specific inhibitor. These findings suggest that calpain might play a role in age-related degradation of the lens cytoskeleton.