Abstract Gossypol, a polyphenolic compound isolated from cotton plant was found to degrade pBR322 DNA in vitro in a reaction which required the presence of a metal ion, a reducing agent (2-mercaptoethanol) and oxygen as revealed after agarose gel electrophoresis. Fe 3+ and Co 2+ showed maximum degradation whereas addition of Ca 2+ and Mg 2+ prevented the gossypol mediated DNA damage. Gossypol caused degradation of rat liver DNA incubated in vitro even in the absence of added metal ions and 2-mercaptoethanol. Incubation of intact rat liver nuclei with gossypol reveled DNA degradation and nuclei isolated from rats treated with gossypol in vivo showed higher succestibility to DNA fragmentation when incubated with gossypol in vitro than control nuclei. EcoRl and AIuI digestion of DNA isolated from gossypol treated rats gave clear cut evidence for DNA degradation. These observations indicate that gossypol is genotoxic and considereable care has to be exercised in its use.