Several ribosome-inactivating proteins (RIPs), such as ricin (including its A-chain), luffin, cinnamomin and camphorin, were found to express enzymatic activity to cleave supercoiled double-stranded DNA. In particular, alpha-sarcin, a RIP with a novel ribonuclease activity, was first proved to have this activity. They convert supercoiled DNA into a nicked circular conformation at low concentrations and further into a linear form at high concentrations: they have no effect on linear DNA. Although intact type II RIPs exhibited no RNA N-glucosidase activity, they were detected to cleave supercoiled DNA. Even if ricin A-chain was treated by boiling, its activity on supercoiled DNA was largely retained.